FIZIOLOGIA
physiology
FRANCISC SCHNEIDERCARMEN PANAITESCUCARMEN TATUFLORINA BOJINMIHAI NECHIFORSORIN RIGAGABRIELA TANASIEDACIANA NISTORCALIN MUNTEAN

FOUNDING EDITORCHIEF EDITOR
CO-CHIEF EDITORSASSOCIATE EDITORSEXECUTIVE EDITORSEDITORIAL BOARD
ARDELEAN AURELBĂDĂRĂU ANCA
BENEDEK GYORGYBENGA GHEORGHEPANAITESCU CARMEN
COJOCARU MANOLE(Arad)(Bucureşti)(Szeged)(Cluj)(Timişoara)(Bucureşti)PETROIU ANARÂCZ OLIVERRIGA DANSABĂU MARIUS
SIMIONESCU MAIA
SAULEA I. AUREL

IANCAU MARIAMIHALAŞ GEORGETA
MUNTEAN DANINAMUREŞAN ADRIANANESTIANU VALERIUOPREA TUDOR
PĂUNESCU VIRGIL(Craiova)(Timişoara)(Timişoara)(Cluj)(Craiova)(New Mexico)(Timişoara)

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Fiziologia - Physiology • 2015.25.3(87)The 29th National Conference of the Romanian Society of Physiological Sciences with international attendance“Personalized Physiology from Concept to Precision Medicine”, Timisoara, 25 – 27 May 2017

The largest Romanian conference of Neuroscience andPhysiology with international participation:

From brain to heart and back

September 29th - October 1st, 2022
Venue:
Faculty of Medicine,
Carol Davila University of Medicine and Pharmacy
8 Eroii Sanitari Blvd., 050474 Bucharest, Romania

Fiziologia - Physiology • 2022. SUPPLEMENT 1

The largest Romanian conference of Neuroscience and Physiology with international participation:
From brain to heart and back, Bucharest, September 29th - October 1st, 2022

Sponsors & Partners

The largest Romanian conference of Neuroscience and Physiology with international participation:
From brain to heart and back, Bucharest, September 29th - October 1st, 2022

The National Neuroscience Society of Romania(SNN) was founded in 2000 in Bucharest.
From the very beginning, SNN was affiliated to theFederation of European Neuroscience Societies(FENS) and to the International Brain Research
Organization (IBRO), through its former “Central andEast European Regional Chapter” (CEER), presently
part of the “Pan-European Regional Chapter” (PERC),
aimed at helping neuroscience in the region. SNN iscontinuing to win the support of IBRO for organizing
its national meetings with international participation.
SNN webpage: www.snn.ro

The Romanian Society of Physiology (SRF) was
founded in 2009 in Cluj-Napoca.
SRF is affiliated to the Federation of European
Physiological Societies (FEPS) and to theInternational Union of Physiological Sciences (IUPS).
SRF webpage: www.fiziologie.org

4

Fiziologia - Physiology • 2017. SUPPLEMENT 1

The largest Romanian conference of Neuroscience and Physiology with international participation:
From brain to heart and back, Bucharest, September 29th - October 1st, 2022

O rg an iz in g com mit te e
Mihai Moldovan M.D. Ph.D. (București) – President of the National Neuroscience Society of Romania (SNN)Dan Dobreanu M.D. Ph.D. (Târgu-Mureș) – President of the Romanian Society of Physiology (SRF)
Ana-Maria Zăgrean M.D. Ph.D. (București) – Chair of the Organizing Committee, SNN General Secretary,
SRF Scientific Secretary
Leon Zăgrean, M.D. Ph.D. (București) – Honorary President of the National Neuroscience Society of Romania
Carmen Panaitescu M.D. Ph.D. (Timișoara) – Past President of the Romanian Society of Physiology
Aurel Popa, Ph.D. (Craiova) – Vice-President of the National Neuroscience Society of Romania
Simona Clichici M.D. Ph.D. (Cluj Napoca) – SRF General Secretary
Alina Scridon M.D. Ph.D. (Târgu Mureș) – SRF Executive Secretary
Gabriela Adriana Filip M.D. Ph.D. (Cluj Napoca) – SRF Treasurer
Tibor Szilágyi, M.D. Ph.D. (Târgu-Mureș) – SNN Board member
Tudor-Adrian Bălșeanu, M.D. Ph.D. (Craiova) – SNN Board member
Bogdan Pavel M.D., Ph.D. (București) – SNN Board member
Denise Carmen Mihaela Zahiu M.D., Ph.D. – SNN Treasurer

Scientific committee

Local organizing committee

Chairs of the Scientific Committee:

Ioana Ștefănescu M.D. Ph.D.
Adrian Eugen Roșca M.D. Ph.D.

Dan Dobreanu M.D. Ph.D. (Târgu-Mureș)Mihai-Aurelian Ghiță M.D. Ph.D.

Mihai Moldovan M.D. Ph.D. (București)Monica Giurgiu M.D. Ph.D.
Cristina Goanță M.D. Ph.D.

Members of the Scientific Committee:

Sebastian Isac M.D. Ph.D.
Daniela Iliescu M.D. Ph.D.

Ana-Maria Zăgrean M.D. Ph.D. (București)Mihai Stancu M.D. Ph.D. Stud.

Adelina Vlad M.D. PhD. (București)Alexandru-Cătălin Pâslaru M.D., Ph.D.

Violeta Ristoiu Ph.D. (București)Vlad-Petru Morozan, M.D. Ph.D. Stud.

Alexandru Babeș Ph.D. (București)Alina Scridon M.D. Ph.D. (Târgu-Mureș)Editorial committee

Simona Clichici M.D. Ph.D. (Cluj Napoca)
Ionela Lăcrămioara Șerban M.D. Ph.D. (Iași)Ana-Maria Zagrean M.D., Ph.D.

Carmen Tatu M.D. Ph.D. (Timișoara)

Mihai Stancu M.D. Ph.D. Stud.

Dana Carmen Zaha M.D., Ph.D. (Oradea)

Marius Georgescu M.D. Ph.D. (Timișoara)

Fiziologia - Physiology • 2022. SUPPLEMENT 1

The largest Romanian conference of Neuroscience and Physiology with international participation:
From brain to heart and back, Bucharest, September 29 th - October 1st, 2022
Organizers:
National Neuroscience Society of Romania & Romanian Physiology Society
in partnership with Carol Davila University of Medicine and Pharmacy and IBRO
Venue:
Faculty of Medicine, Carol Davila University of Medicine and Pharmacy
8 Eroii Sanitari Boulevard, Bucharest
Event type: onsite
Event official languages: Romanian and English; presented materials in English

ProgramThursday, 29.09.2022
13:00 - 14:00 Onsite registration and poster mounting
14:00 - 15:00 Satellite workshop – Dizzy Workshop – investigating vestibular system. Organizers: DanielaCîrpaciu, Cristina Maria Goanță
15:00 - 15:30 Opening Ceremony
15:30 – 17:15 Session 1, Chairs: Marius Sabău, Dan Dobreanu
Marius Sabău – “Gheorghe Arsenescu” Lecture
Ruxandra Drăgoi-Galrinho - Experimental echocardiography
Alkora-Ioana Balan – Impact of chronic ivabradine administration on autonomic nervous system
Vasile Bogdan Halațiu – Impact of Bisphenol A on the cardiovascular system
Florentina Pluteanu – Altered subcellular Ca2+ signaling in atrial myocytes of hypertensive rats
Andreas Rinne - Allosteric modulation of GPCR signaling by the membrane potential
17:15 – 17:30 Coffee break
17:30 – 19:30 Session 2, Chairs: Mihai Moldovan, Tibor Szilágyi
Mihai Moldovan - “Mircea Steriade” Lecture. The infraslow brain activity matters
Andrei Barborică - Validation of EEG source localization algorithms through simultaneous scalp-intracranial EEG
recordings in patients with drug-resistant epilepsy
Miralena Tomescu - Oxytocin modulates salience associated resting EEG microstates
Tudor Badea - Selective molecular markers for Retinal Ganglion Cell anatomy, physiology and function
Mihai Stancu - Acoustic stimulation tunes axonal conduction speed by regulating radial growth of myelin on an
individual axon-to-axon basis
19:30 – Welcome cocktail

Friday, 30.09.2022

8:30 – 9:00 Onsite registration and poster mounting
09:00 - 10:30 Session 3, Chairs: Carmen Panaitescu, Ana-Maria Zagrean
Bogdan Pavel - “Nicolae C. Paulescu” Lecture - Do we need near infrared spectroscopy and end-CO2 monitoring
during hyperventilation test?
Constantin Căruntu - Neuro-endocrine factors in the skin - from physiology to pathological conditions
Carmen Panaitescu – Allergies in a changing world
Carmen Tatu - Prediction of allergic response based on molecular components
Gabriela Tănasie - Aeroallergens impair the barrier function of the bronchial epithelial cells - an in vitro study
Michael Bogdan Mărgineanu - Consensus strategy for B cell epitope prediction in allergen IgE epitope mapping
studies
10:30 - 11:00 Coffee break
11:00 – 12:30 Session 4, Chairs: Leon Zăgrean, Ionela Lăcrămioara Șerban
Ionela Lăcrămioara Șerban - “Ion Haulică” Lecture
Dragomir Șerban - Endothelial function vs. oxidative stress: molecular mechanisms
Radu Iliescu - Neural control of blood pressure: therapeutic target for hypertension
Minela Mărănducă - News in the renin-angiotensin system
Andrei Neamţu - Applications of computer simulation methods in molecular physiologyIonuţ Tudorancea - The role of inflammatory cytokines in obesity hypertension
12:30 - 12:45 Sponsor presentation
12:45 - 13:30 Lunch
13:30 - 15:00 - Poster session & Young investigators blitz presentations
15:00 - 16:30 Session 5, Chairs: Gabriela Adriana Filip, Dana-Carmen Zaha
Simona Clichici - “Mircea Doroftei” Lecture
Mihai Lupu - Effect of iron redistribution in an experimental model of cardiac hypertrophy
Iuliana Nenu - Trusting your gut – a new paradigm in hepatocellular carcinoma therapy
Irina Camelia Chis - Quercetin restores endothelial dysfunction in diabetic rat aortic rings
Nadina Liana Pop - Magnetic nanoparticles functionalized with chitosan: between nerve regeneration of
peripheral nerve injuries and hepatotoxicity
Diana Valentina Tudor - Celecoxib: a double-edged sword in metastatic melanoma
16:30 – 17:00 Coffee break
17:00 – 18:30 Session 6, Chairs: Alexandru Babeș, Violeta Ristoiu
Maria Luisa Flonta - “Dimitrie Călugăreanu” Lecture
Beatrice Radu - Assessing the safety profile of a drug - an itinerary from heart to brain
Bogdan Amuzescu - Infrared laser effects on excitability of primary sensory neurons and gating of Nav1.5 ionchannelsDebora-Elena Huțanu - The antimalarial artemisinin is a non-electrophilic agonist of the Transient Receptor
Potential Ankyrin type 1 receptor-channel
Roxana-Olimpia Gheorghe - Switch of macrophages to M2 phenotype after cytoskeleton alteration reduces SNL
induced neuropathic pain
Tudor Șelescu - TRPM8-dependent 'wet dog shake' behaviour in mammals and birds
18:30 - 19:30 - General Assembly of SRF
19:30 - 20:30 - General Assembly of SNN

Saturday, 01.10.2022 – Brain Day – IBRO Sessions
09:00 – 10:30 Session 7 – IBRO session, Chairs: Aurel Popa-Wagner, Tudor-Adrian Bălșeanu
Tudor-Adrian Balseanu - “Valeriu Neștianu” Lecture. Obesity as a risk factor for cerebrovascular disease:biomarkers and back-translation into animal models for development of novel therapies
Bogdan Catălin - The Impact of Acute Sepsis on Amyloid Formation in a Mouse Model of Alzheimer’s Disease
Roxana Surugiu - Brain exosomal vesicles as serum biomarkers of stroke
Aurel Popa-Wagner - Long-term treatment with chloroquine increases lifespan in middle-aged male micepossibly via autophagy modulation, proteasome inhibition and glycogen metabolism
Dirk Hermann - Injury development and therapeutic responses to small extracellular vesicles in the aged
ischemic brain
10:30 – 10:45 Coffee break
10:45 – 12:30 Session 8, Chairs: Beatrice Radu, Tudor Badea
Leon Zăgrean - “Gheorghe Marinescu” Lecture
Ana-Maria Zăgrean – Brain response to perinatal asphyxia in experimental paradigms
Sebastian Isac - The impact of general anesthesia on the developing brain previously exposed to perinatal
asphyxia
Mara-Ioana Iesanu - The impact of gestational gut microbiome alteration on neurodevelopment in rat offspring
exposed to perinatal asphyxia
Violeta-Maria Caragea - Dopaminergic modulation of hippocampal synaptic plasticity and spatial memory
Diana Rotaru - MR spectroscopy of GABA and glutathione: advancements in data acquisition, preprocessing andanalysis.
Gabriel Crumpei - The information paradigm in neuroscience
12:30 – 12:45 Coffee break
12:45 - 14:00 Session 9 (SNN SRF Roundtable) - Brain Day - IBRO event, Chairs: Ana-Maria Zăgrean, Mihai
Moldovan
14:00 – 15:00 Concluding remarks, Awards, and Closing Ceremony
The sessions are scheduled in G.E. Palade Amphitheater, except Sessions 3 and 4 which will take place in theCouncil Hall.
Fiziologia - Physiology • 2022. SUPPLEMENT 1

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ABSTRACTS - ORAL PRESENTATIONS
O1. Impact of chronic ivabradine
administration on autonomic nervous system

O2. Altered subcellular calcium signaling
in atrial myocytes of hypertensive rats

Balan Alkora-Ioana (1,2), Halațiu Vasile Bogdan (1),
Cozac Dan Alexandru (1,2), Mutu Cosmin
Constantin (1), Comșulea Emilian (1), PerianMarcel (1), Scridon Alina (1,3)

Florentina Pluteanu (1); Jens Kockskämper (2)(1) Department of Physiology, Faculty of Medicine, Universityof Medicine, Pharmacy, Science and Technology “George
Emil Palade” of Târgu Mureș, Romania (2) Department of
Cardiology, Emergency Institute for Cardiovascular Diseases
and Transplantation, Târgu Mureș, Romania (3) Center for
Advanced Medical and Pharmaceutical Research, TârguMureș, Romania

The mechanisms underlying the modulation of the If
current by the autonomic nervous system (ANS) are
well understood. In contrast, the effects of chronic If
blockade on the ANS are still largely unknown. We
thus aimed to evaluate the effects of chronicivabradine therapy on cardiac autonomic modulation.
Adult male Wistar rats were randomized into twogroups: Control (n = 6) and IVA (ivabradine 10
mg/kg/day, 3 weeks, n = 10). All rats were implantedwith radiotelemetry ECG devices and 24-h continuous
ECG monitoring was performed. Heart rate variability
analysis was performed. The parameters that estimate
the activity of the parasympathetic and sympathetic
nervous systems, as well as the balance between thetwo components were analyzed. As expected, mean
24-h heart rate was significantly lower in the IVA
compared to the Control rats (p< 0.01). Parametersreflecting vagal activity were significantly higher in IVA
compared to Control rats (all p >0.05). In the IVA rats
sympatho-vagal balance was shifted toward vagal
dominance (p = 0.04). These changes were present
both when the animals were awake and while asleep(all p< 0.05). Our study demonstrates that chronic
administration of ivabradine increases vagal
modulation and shifts ANS activity toward vagal
dominance in healthy rats, bringing new insights into
the mechanisms of ivabradine-related atrial
proarrhythmia. By increasing parasympathetic tone inhealthy rats, this study suggests that the vagal
dominance induced by ivabradine extends beyond
heart failure, and it can be used in other clinicalconditions associated with increased sympathetic
activity.

(1) Department of Anatomy, Animal Physiology andBiophysics, Faculty of Biology, University of Bucharest,
Bucharest, Romania; (2) Institute of Pharmacology andClinical Pharmacy, Biochemical and Pharmacological Center(BPC) Marburg, Philipps-University Marburg, Marburg,
Germany

Hypertension (HTN) is a major risk factor for
cardiovascular complications, such as heart failure andatrial fibrillation. At the atrial level, the cellular andmolecular mechanisms of HTN-induced functional
remodeling are insufficiently understood. Our
hypothesis was that altered calcium signaling occur inspontaneously hypertensive rats (SHR) and contributeto aggravation of the functional remodeling and AF
susceptibility. Here, we characterized the calcium
handling mechanisms in atrial myocytes isolated from
SHR or age-matched normotensive Wistar-Kyoto(WKY) control rats, at different stages of HTN: (1)young with developing left ventricular hypertrophy(LVH), (2) mature with stable HTN and compensatory
LVH, and aged rats (3) with no heart failure or (4) withheart failure. Confocal microscopy was used toinvestigate the subcellular calcium transients
electrically evoked, while patch clamp was used torecord the L-type calcium current and Na+/Ca2+
exchanger current during compensatory LVH stage.
The functional measurements were correlated with thelevels of calcium -handling proteins in the atria of thesame experimental groups. Our results obtained fromatrial myocytes of SHR showed that subcellularalterations of calcium signaling were mostly localized at
sub-sarcolemmal and sarcolemma level and correlatewith the expression and phosphorylation of thecalcium-handling proteins. Experimental simulation oftachycardia induced significantly more arrhythmogenic
calcium alternans in SHR than in WKY atrial myocytes.
These data indicate that in the context of HTN, thesubcellular changes in calcium signaling may represent
an important substrate for the increased propensity of
SHR to develop atrial tachyarrhythmias.
Funding: EUTRAF

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O3. Allosteric modulation of GPCR
signaling by the membranepotential

O4. The infraslow brain activity matters
Mihai Moldovan (1,2,3)

Andreas Rinne
Department of Biophysics and Cellular Biotechnology,
UMFCD Bucharest, Bucharest, Romania
G-protein-coupled receptors (GPCRs) are one of thelargest classes of cell surface receptors. They regulate
multiple cellular functions and represent important drug
targets. Allosteric modulation of GPCRs refers to achange of signaling of preactivated receptors induced bysmall molecules known as allosteric modulators (AMs).
Classic AMs bind to the receptor at intracellular or
extracellular sites different from the orthosteric bindingsite for agonists. AMs either facilitate activation of thereceptor (positive allosteric modulation) or cause
inhibition (negative allosteric modulation). It is now
recognized that class A GPCRs are voltage dependent.
By using fluorescent biosensors that resolve receptor
activation (conformational changes) or receptor
signaling (G-protein activation) we demonstrate that thenovel phenomenon of voltage dependence serves as anallosteric modulator of GPCRs. Our data suggest thatthe molecular pathway that alters receptor activity inresponse to voltage involves intracellular andextracellular binding sites of known AMs. Remarkably
similar to pharmacological allosteric modulation, a
depolarization of the membrane modulated binding of
the orthosteric agonist and affected G protein signaling.
These effects translated into fine-tuning of cellularsignaling events downstream of the receptors.
Consequently, pharmacological properties and signalingof receptors expressed in electrically excitable cells
differ from those observed in non-excitable cell types.
Funding: DFG (German Research Society).

(1) Department of clinical neurophysiology, Rigshospitalet,
Copenhagen, Denmark; (2) Department of neuroscience, Universityof Copenhagen, Denmark; (3) Department of Functional Studies,
Division of Physiology, Center for Excellence in Neuroscience,
University of Medicine and Pharmacy Carol Davila, Bucharest,
Romania

An oscillatory activity can be recorded from many
cortical networks across brain states and species. The
resulting fluctuations in the scalp electromagnetic fieldrecorded by electroencephalography (EEG) are
typically described within the 1-30 Hz frequency band.
Nevertheless, recordings from single cortical neurons
revealed slower subthreshold oscillations of theirmembrane potential. Functional imaging studies foundthat multiple resting‐state networks, among which themost notorious is the default mode network, present an
infralow activity (ISA) within 0.01-0.1 Hz. It remains
controversial whether the ISA is an epiphenomenon orwhether it serves a physiological function. I propose anovel conceptualization of ISA as a modulatory rhythmof the faster neuronal activity. Data was aggregatedfrom 3 sources: 1) cortical EEG recordings in rats
under deep anesthesia subjected to intermittent photic
stimulation or auditive stimulation; 2) scalp EEG
recordings at rest from healthy volunteers and poststroke comatose patients during photic or verbal
stimulation and 3) in vivo Ca2+ imaging from thepyramidal neurons of the mouse prefrontal cortex
during a go/no-go behavioral task. These data suggestthat ISA coalesces the faster neuronal activity into
oscillatory macrostates. The modulatory strength of
ISA appeared stronger when the specific input was
reduced. Such a subthreshold effect could matter for
behavior in conditions of uncertainty.
The macrostate EEG analysis is protected underpatent EP3646784B1
Funding: This project was partly supported by grants of
the Romanian National Authority for Scientific
Research, CNCS – UEFISCDI, project number PN-IIID-PCE-2011-3-0847, PN-II-PT-PCCA-2011-3.2-1290
and PN-III-P2-2.1PTE-2016-0114.

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O5. Validation of EEG source localization
algorithms through simultaneous scalp-intracranial
EEG recordings in patients with drug-resistant
epilepsy
Andrei Barborică (1), Ioana Mîndruță (2), Irina
Oane (2), Cristian Donoș (1), Felicia Mihai (1),Constantin Pistol (1)(1) Physics Department, Bucharest-Măgurele,
Romania; (2) Epilepsy Monitoring Unit,
Neurology Department, Emergency University
Hospital Bucharest, Bucharest, Romania
Funding: UEFISCDI COFUND-FLAGERA IISCALES, PN-III-P4-ID-PCE-2020-0935

O6. Intranasal oxytocin modulatessalience microstates as a function ofsocial proficiency
Miralena I. Tomescu(1,2,3), Stephanie Van der
Donck (4,5), Emanuela M. Perisanu (6,7), Valeria
Kebets (8), Alexandru I. Berceanu (2), Kaat Alaerts(4), Bart Boets (4,5) and Ioana Carcea (1,2,9);Andrei Popescu (2)(1) Faculty of Educational Sciences, Department of
Psychology, University “Stefan cel Mare” of Suceava,
Bucharest, Romania; (2) CINETic Center, National Universityof Theatre and Film “I.L. Caragiale” Bucharest, Bucharest,
Romania; (3) Faculty of Psychology and Educational
Sciences, Department of Psychology, University of Bucharest,
Bucharest, Romania; (4) Center for Developmental
Psychiatry, Department of Neurosciences, KU Leuven,
Belgium; (5) Leuven Autism Research (LAuRes), KU Leuven,
Leuven 6.Institute of Cardiovascular Diseases, Timisoara,
Romania; (7) Faculty of Medicine, University of Sibiu, Sibiu,
Romania; (8) Department of Electrical and Computer
Engineering, National University of Singapore, Singapore; (9)Department of Pharmacology, Physiology and Neuroscience,
Rutgers Brain Health Institute, Rutgers, The State Universityof New Jersey

Intranasal oxytocin (OXT) administration is considered
as a potential treatment for social cognition as it
modulates social behavior by possibly enhancing
salience towards social stimuli as a function of social
context. Inter-individual variability in expectations
about the social context, social behavior patterns andassociated intrinsic spontaneous brain activity mightplay an important role in salience attribution that drives
behavior. With this goal we investigated modulatory
effects of exogenous OXT on fast dynamics of
spontaneous EEG activity as a function of self-reported
social responsiveness, social phobia and adultattachment using multivariate partial least square(PLS) statistical analyses. For each condition we
identified seven EEG microstates, very similar between
conditions (OXT vs placebo (PLCB)) and to theprototypical EEG microstates previously reported in theliterature. In line with Schiller et al., 2019 we confirm
an increased stability for D but also F EEG microstates
after OXT administration. However, we also founddecreased duration and occurrence for C and E

microstates. In the narrow frequency band analyses wefound modulations for the A (delta 2-4Hz), B (lowgamma 30-40Hz) and G (delta and low gamma)
microstates. Effects of the OXT administration on the
low gamma frequency band microstate dynamics(OXT-PLCB) showed that D and F increased durationand occurrence was most prominent in the low
secure/high anxiety/high avoidance attachment style,and/or high social phobia, and/or low motivation selfreported social responsiveness. The opposite was true
for C and E microstates, where decreased
duration/occurrence was most prominent for highsecure/low anxiety and avoidance, and/or low social
phobia, and/or high social responsiveness individuals.
These results suggest differential OXT effects on
spontaneous dynamics of EEG microstates as afunction of social attachment style and social
responsiveness. Exogenous OXT might increase
attention and salience related network dynamics (Dand F microstate, respectively) in individuals with
impaired social skills and difficulties in social
attachment, and might decreased default-mode
network dynamics (C and E microstate, respectively)
for the socially high responsive, and secure attachment
style individuals. This result supports the socialsalience enhancement hypothesis as a possible
mechanism by which OXT is modulating behavior and,to a higher degree in socially less responsive
individuals. Moreover, these results might partiallyexplain contradictory behavioral effects of OXT that
can act via different temporal patterns of spontaneous
EEG microstate. Social motivation, attachment style,social phobia among other social traits might drivesocial expectations towards most likely social
scenarios to ensure best adapted behavior bydifferentially modulating dynamics of EEG microstates
after OXT administration.
Funding: The project “Developing a methodology oftherapy through theater with an effect at theneurochemical and neurocognitive levels” (MET) is
financed by the European Regional Development Fund(ERDF) through Competitiveness Operational Program
2014–2020, SMIS code 106688 and implemented by
UNATC “I.L. Caragiale”, CINETic center, LDCAPEILAB. First author was also funded by an International
Brain Research Organization (IBRO) fellowship.
Additionally, the study was also funded by an
European Economic Area (EEA)/Norway grant, EEAROsingle bondNO-2018–0606.ed13

O7. Acoustic stimulation tunes axonal
conduction speed by regulating radial
growth of myelin on an individual axontoaxon basis
Mihai Stancu, Conny Kopp-Scheinpflug
Division of Neurobiology, Department of Biology &Graduate School of Systemic Neurosciences, LudwigMaximilians University, Munich, Germany

Funding: DFG SFB870 A-10

O8. Do we need near infrared spectroscopy
and end-tidal CO2 monitoring duringhyperventilation test?
Bogdan Pavel (1), Ștefan Șandru (1), Denise
Carmen Mihaela Zahiu (1), Sebastian Isac (1, 2),
Ana-Maria Zagrean (1)(1) Division of Physiology, Department of Functional
Sciences, “Carol Davila” University of Medicine andPharmacy, Bucharest, Romania; (2) Department ofAnesthesiology and Intensive Care I, ‘Fundeni’ ClinicalInstitute, Bucharest, Romania

Background: The purpose of this study was to assess
the role of end-tidal CO2 (ETCO2) monitoring duringhyperventilation in predicting the occurrence of
cerebral oximetry changes, recorded by near-infrared
spectroscopy (NIRS). Materials and Methods: Forty-six
healthy volunteers were enrolled in the study. All
subjects were required to breathe at a baseline rate (814 breaths/min) for the first 2 minutes of the procedureand then to hyperventilate at a double respiratory rate
for the next 4 minutes. The parameters monitored
during the test were: the regional cerebral
oxyhemoglobin and deoxyhemoglobin concentrations
via NIRS, ETCO2 and the respiratory rate. Results:
During hyperventilation, each subject showed adecrease in ETCO2 values comparing with baseline.
Only the subjects (N=30) who registered a reduction(%) in ETCO2 of 37.58% ± 10.34% presented changes
in cerebral oximetry. These oximetry changes wererepresented by a decrease in total hemoglobin andoxyhemoglobin concentrations whereas reduced
hemoglobin remained unchanged. Using the AUCROC analysis, an ETCO2 decrease > 26% was
identified as the optimal cutoff value for predicting theoccurrence of changes in cerebral oximetry (AUC-ROC= 0.93, p < 0.0001). Conclusions: Cerebral
vasoconstriction induced by hyperventilation cannot beeffectively predicted by the rise in the respiratory rate
alone. Therefore, the simultaneous ETCO2 andcerebral oximetry monitoring could be used to validate
this clinical test.

O9. Neuro-endocrine factors in the skin – fromphysiology to pathological conditions
Constantin Caruntu (1,2); Mihaela Adriana Ilie (3);Daniel Boda (2,4); Ana Caruntu (5,6)(1) Department of Physiology, “Carol Davila” University of
Medicine and Pharmacy, Bucharest, Romania; (2)Department of Dermatology, “Prof. N. Paulescu” National
Institute of Diabetes Nutrition and Metabolic Diseases,
Bucharest, Romania; (3) Dermatology Department, Kalmar
County Hospital, Kalmar, Sweden; (4) Dermatology ResearchLaboratory, “Carol Davila” University of Medicine andPharmacy, Bucharest, Romania; (5) Department of Oral andMaxillofacial Surgery, “Carol Davila” Central Military
Emergency Hospital, Bucharest, Romania; (6) Department ofOral and Maxillofacial Surgery, Faculty of Dental Medicine,“Titu Maiorescu” University, Bucharest, Romania.

The structure of the skin is extremely complex, withseparate layers, of different embryological origin, butfunctionally interdependent. The regulation of skinfunctions involves numerous mechanisms, with cellularand molecular details that still need to be unveiled.
Various types of neurohormones, neuropeptides,
neurotransmitters and neuromediators are released
both by the cutaneous nerve fibers and by numerous
skin cells. The activation of their receptors contributes
to the modulation of physiological andpathophysiological processes that may remain local or
may affect the entire body. Knowledge of theinterconnections between the nervous system and theskin can contribute to the discovery of new functional
mechanisms and new therapeutic targets. Moreover, it
can have an important clinical impact through thedevelopment of new approaches in the treatment ofskin diseases. This work was supported by a grant of
the Ministry of Research, Innovation and Digitization,
CCCDI - UEFISCDI, project number PN-III-P2-2.1PED-2021-2243, within PNCDI III
Funding: This work was supported by a grant of the
Ministry of Research, Innovation and Digitization,
CCCDI - UEFISCDI, project number PN-III-P2-2.1PED-2021-2243, within PNCDI III

14

O10. Allergies in a changing world
Carmen Panaitescu (1,2), Roxana Buzan (1,2),
Lauriana‐Eunice Zbîrcea (1,2), Camelia-Felicia
Banarescu (2), Kuan‐Wei Chen (2), Virgil Păunescu(1,2)(1) Center of Immuno‐Physiology and Biotechnologies,
Department of Functional Sciences, Victor Babes Universityof Medicine and Pharmacy, Timisoara, Romania; (2)OncoGen Center, Pius Brinzeu County Clinical Emergency
Hospital, Timisoara, Romania.

Background: A healthy immune response to allergen ischaracterised by allergenspecific T cell tolerance,
induced spontaneously by dose-dependent exposure
to allergens. Tolerance induction is maintained byregulatory T cells secreting IL-10 and TGF-β, IgG4synthesis and inhibition of allergic effector cells.
Allergic response is characterised by a Th2-immune
response, especially in atopic individuals, under the
influence of genes and environmental factors. Allergic
sensitisation is driven by type 2 specific cytokines(including IL-4 and IL-13, essential for IgE isotype
switch in B cells, and IL-5, essential for eosinophilic
inflammation), allergen-specific IgE, andallergenspecific Th2 and B memory cells. The
allergens have multiple epitopes, able to induce
specific-IgE synthesis, each one favouring the allergic
response to another epitope, in a process of“molecular spreading”. Ragweed pollen contains 12
molecular allergens, with Amb a1 and Amb a 11 as
major allergens. The aim of our study was toinvestigate IgE reactivity profiles of ragweed allergic
patients and to associate them with clinical symptoms.
Methods: IgE sensitization profiles from clinically well‐characterized ragweed allergic patients (n = 150) wereanalyzed using immunoblotted ragweed pollen extract.
Immunoblot inhibition experiments were performed
with two Amb a 1 isoforms and CCD markers, andbasophil activation experiments were performed with
IgE serum before and after depletion of Amb a 1‐
specific IgE. Results: 19 different IgE reactivity
patterns with and without Amb a 1‐sensitization wererevealed by immunoblotting. Serum with and without
Amb a 1‐specific IgE induced basophil activation.
Patients with complex IgE sensitization profiles
developed more clinical symptoms.

O11. Prediction of allergic response based onmolecular components
Carmen Tatu (1,2); Laura Haidar (1), Maria-Roxana
Buzan (1,2); Manuela Grijincu (1,2); Lauriana
Zbircea (1,2); Gabriela Tănăsie (1,2); Carmen
Panaitescu (1,2)(1) Department of Functional Sciences, Physiology, Center of
Immuno-Physiology and Biotechnologies (CIFBIOTEH),“Victor Babeș” University of Medicine and PharmacyTimișoara, Romania; (2) Centre for Gene and Cellular
Therapies in The Treatment of Cancer - OncoGen, “Pius
Brinzeu” Clinical Emergency Hospital, Timisoara, Romania

Traditionally, the diagnosis of allergic diseases has
been based on a thorough clinical history together with
proof of sensitisation to allergens, either in vivo, by skinprick test and/or in vitro, by identification of serum
specific immunoglobulin E. Both in vivo and in vitro
evaluation of the sensitisation status are extract-based
methods, which often fail to identify the molecules
responsible for the allergic reactions, as the extractcontains a mixture of allergenic molecules, somecommon to multiple sources (cross-reactive molecules
or pan-allergens) while other allergenic molecules are
specific to a singular source (genuine or speciesspecific allergens).Component resolved diagnosis
developed in the last twenty years, has overcome mostof these limitations, as it distinguishes molecularallergens responsible for symptom elicitation fromthose attributable to cross-reactivity. This diagnostic
strategy is evolving towards the new concept ofprecision immunology for allergy diagnosis, which aims
to improve the management of allergic diseases andasthma. The benefits of using molecular components
are: better diagnosis for symptoms elicited bymolecules of low abundance and/or weak stability thus
missing in the extract; risk assessment in food and/or
venom allergy; indicator of cross-reactivity; marker ofgenuine (species specific) sensitization. In addition,
component-resolved diagnosis can support the choiceof allergen immunotherapy based on patientsensitization profiles. Emerging applications ofcomponent-resolved diagnosis are focused on
characterizing allergic diseases and asthma endotypes
and in the diagnosis of occupational allergic disease.

15

O12. Aeroallergens impair the barrier functionof the bronchial epithelial cells - an in vitro
study

O13. Consensus strategy for B cell epitope
prediction in allergen IgE epitope mapping
studies

Gabriela Tănăsie (1,2); Razvan Ionut Zimbru (1);
Manuela Grijincu (1,2); Bogdan Michael
Margineanu (1); Lauriana Eunice Zbircea (1,2);
Roxana Maria Buzan (1,2); Laura Haidar (1);
Carmen Tatu (1,2); Carmen Panaitescu (1,2)

Michael B. Mărgineanu (1); Virgil Păunescu (1,2);
Carmen Panaitescu (1,2)(1) Department of Functional Sciences, Physiology, Center of
Immuno-Physiology and Biotechnologies (CIFBIOTEH),“Victor Babeș” University of Medicine and PharmacyTimișoara, Romania; (2) Centre for Gene and Cellular
Therapies in the Treatment of Cancer - OncoGen, “Pius
Brinzeu” Clinical Emergency Hospital, Timisoara, Romania;

The respiratory epithelium acts as a complex barrier at
the interface between the ventilated air and thebronchial structures. Respiratory viruses and pollutants
affect the integrity of the epithelial layer, causing
inflammatory reactions and inducing hyper-reactivity ofthe bronchial smooth muscle. The present study
investigated the in vitro interactions of aeroallergens
with the bronchial epithelium, addressing the mainindoor allergen, house dust mite (HDM), and one of themost effective outdoor allergens, ragweed pollen.A
human bronchial epithelial cell line (NHBE) was
cultured at the air-liquid interface and then exposed todifferent concentrations of standardized extracts of
HDM and ragweed, as well as to the combinations ofallergenic fragments with clinical relevance: Amb a 1,
Amb a 11, Amb a 12 (from Ambrosia pollen), and Der
p 1 (from HDM). The trans-epithelial electricalresistance (TEER) was measured every 30 min for the
first 4 hours, then daily for 72 h. The cellular index of
NHBE cells was monitored 72 h after allergen addition,using an xCELLigence system.The experiments
revealed a substantial decrease in TEER values in thetreated cells, with the largest decrease after
continuous exposure to the combination of HDM andragweed extracts. The alteration of the cellular index
after the addition of combined allergenic fragments
was noticed, especially if ambrosia allergens were
tested after Drp1 exposure.In conclusion, thecombined action of indoor and outdoor allergens can
induce a cumulative effect on the bronchial epithelium,in this way initiating or maintaining the bronchial hyperreactivity state.
INSPIRED Project (INnovative Strategies forPrevention, diagnosis and therapy of ragweed pollen
Induced REspiratory Diseases) - cod SMIS 103662(1) Department of Functional Sciences, Physiology, Center of
Immuno-Physiology and Biotechnologies (CIFBIOTECH),“Victor Babeș” University of Medicine and Pharmacy,Timișoara, Romania; (2) OncoGen Research Center, „Pius
Brinzeu” County Clinical Emergency Hospital, Timisoara,
Romania;

One of the most promising and novel strategies forallergy immunotherapy employs non–IgE-reactive
peptides that are derived from the IgE-binding sites (Bcell epitopes) of the major allergens of a given allergensource. This therapeutic strategy is based on the
induction of blocking IgG antibodies, which prevent theinteraction between IgE antibodies and the allergen. In
silico B-cell epitope prediction methods could help
reduce time and cost of peptide synthesis as typicallyoverlapping synthetic peptides spanning the entire
length of the protein are constructed and evaluated invitro to identify the IgE-binding sites. Based on theprediction results, one can exclude specific peptide
sequences that do not contain any B-cell epitopes
predicted in silico and thus reduce the number ofcandidate peptides that will be synthetized.In thisstudy, we have compared two different consensus
strategies employing two or three of the five prediction
methods Bepipred, BCPreds, ABCPred, Emini,
Kolaskar-Tongaonkar, which exploit the inherent
physicochemical properties of B-cell epitopes in theiralgorithms, or are based on algorithms trained on
epitope and non-epitope data. We have used forvalidation experimental IgE binding inhibition results
obtained for Amb a 8-derived peptides in our group,and reports on other allergen-derived peptides fromliterature. The consensus method employing two tools
predicted epitopes in peptides for which highest IgE
inhibition scores were obtained, and did not predict
potential epitopes in peptides with lowest IgE inhibition,suggesting that this strategy can help reduce thenumber of peptides required for experimental screening
for allergen-specific vaccine development.

16

O14. Endothelial function vs. oxidative stress:
molecular mechanisms

O15. Effect of iron redistribution in anexperimental model of cardiac hypertrophy

Dragomir-Nicolae Șerban, Ionela-LăcrămioaraȘerbanMihai Lupu (1), Diana-Valentina Tudor (1), Ioana
Baldea (1), Vlad-Alexandru Toma (3, 4), Adrian
Florea (2), Ana Lupsor, Remus Moldovan (1),
Nicoleta Decea (1), Gabriela Adriana Filip (1)Physiology Department, “Grigore T. Popa” University of
Medicine and Pharmacy, Iaşi, Romania

There is ongoing wide interest in endothelial function
and dysfunction, in oxidative stress, and in their interrelations. We have been working on such subjects forover ten years. Here we present some of the mostrecent advances in these areas. We discuss the
cardio-vascular physiological responses to stimuli andstress, referring to their variability and reset and also totheir homeostatic, adaptive, and integrative goals. We
focus on the microcirculation, because resistancearteries and arterioles together provide the fineadjustment of local tissue blood flow to the tissue
needs and the main contribution to peripheral
resistance (thus to systemic arterial blood pressure).
Endothelium-dependent relaxation (EDR) of vascularsmooth muscle is known to be mediated by nitric oxide(NO), but the major EDR mechanism in resistancearteries and arterioles is independent of NO-synthaseand cyclooxygenase and it is mediated byendothelium-dependent hyperpolarization (EDH).
EDH-mediated EDR relies on endothelial Ca2+activated K+ channels with small and intermediate
conductance. EDH-mediated EDR is: counter-regulatorof sympathetic vasoconstriction; important in flow
autoregulation, myogenic response, and vasomotion;compensatory in endothelial dysfunction, but also
involved in its pathogenesis. H2O2 has a special rolein EDH-mediated EDR, so here we discuss our very
recent studies on small arteries and the effects of:
H2O2, vitamin C, Mg2+. We also discuss the mostrecent progress in: NO-mediated EDR, endothelial
dysfunction of large arteries, and atherosclerosis.
Therein, our recent clinical studies and reviews havetheir own major focuses: (a) cerebral circulation andfunction; (b) chronic kidney disease.

1 Iuliu Hatieganu University of Medicine and Pharmacy, Dept.
of Physiology, Cluj-Napoca, Romania; 2 Iuliu Hatieganu
University of Medicine and Pharmacy, Dept. of Cell andMolecular Biology, Cluj-Napoca, Romania; 3 Department of
Molecular Biology and Biotechnologies, Babeș-Bolyai
University, Clinicilor Street No. 4-6, 400000 Cluj-Napoca, Cluj
County, Romania; 4 Institute of Biological Research,
Republicii Street No. 48, 400015 Cluj-Napoca, Cluj County,
Romania

Iron dysmetabolism affects a great proportion of heart
failure patients, while chronic hypertension is one of
the most common risk factors for heart failure anddeath in industrialized countries. Serum data fromreduced ejection fraction heart failure patients show arelative or absolute iron deficiency, whereas cellularmyocardial analyses field equivocal data. An observed
increase in organellar iron deposits was incriminatedto cause reactive oxygen species formation, lipid
peroxidation, and cell death. Therefore, we studied theeffects of iron chelation on a rat model of cardiac
hypertrophy. Suprarenal abdominal aortic constriction
was achieved surgically, with a period of nine weeks toaccommodate the development of chronic pressure
overload. Next, deferiprone (100 mg/kg/day), a lipid
permeable iron chelator, was administered for two
weeks. Pressure overload resulted in increased
inflammation, fibrotic remodeling, lipid peroxidation,left ventricular hypertrophy and mitochondrial ironderangements. Deferiprone reduced cardiac
inflammation, lipid peroxidation, mitochondrial ironlevels, and hypertrophy, without affecting circulatingiron levels or ejection fraction. In conclusion, metallic
molecules may pose ambivalent effects within the
cardiovascular system, with beneficial effects of iron
redistribution, chiefly in the mitochondria.

17

O16. Trusting your gut - a new paradigm inhepatocellular carcinoma therapy

O17. Quercetin restores endothelial
dysfunction in diabetic rat aortic rings

Iuliana Nenu (1,2); Diana Tudor (1); Rares Craciun(2); Horia Stefanescu (2); Bogdan Procopet (2);Zeno Sparchez (2); Ioana Baldea (1); Simona
Clichici (2); Adriana Gabriela Filip (2)Irina-Camelia Chiş (1), Daniela-Rodica Mitrea(1), Remus Moldovan (1), Şoimiţa Suciu (1),Simona Clichici (1)(1) “Iuliu Hatieganu” Univeristy of Medicine and Pharmacy,
Physiology Department, Cluj-Napoca, Romania; (2) Regional
Institute for Gastroenterology and Hepatology “Prof. Dr. O.
Fodor”

Introduction: Hepatocellular carcinoma (HCC) has
become a worldwide burden and its incidence is rising.
The intestinal microbiota is responsible for inducing
resistance to antitumoral drugs. The present study
investigated the effects of the combined treatment ofRegorafenib (Rego) and probiotic Streptococcus
rhamnosus (Pro) on HCC bearing mice. Main methods:
We have induced cirrhosis and hepatocellular
carcinoma on two week Swiss male mice using
diethylnitrosamine (DEN) 1 mg/kg one intraperitoneal
injection following carbon tetrachloride (CCl4) 0.2
ml/kg intraperitoneal administration two times per week
for six weeks. Abdominal ultrasound was performed tovalidate the presence of cirrhosis and liver tumors.
Afterward, the mice were divided into four groups: inthe first group (control group), the mice were only
monitored, the second group received Regorafenib, inthe third group probiotic was administered, and the lastgroup received the combination of Rego and Pro.
Tumour and intestinal inflammation performed by
ELISA and western blot, apoptosis markers, necrosis
rate and oxidative stress markers were assessed.
Results: Although without statistical significance(p>0.05), levels of both Il-6 and Il-1 decreased in thegroups where the probiotic was administered.
Similarly, malondialdehyde levels dropped when Pro
was added. Tumor necrosis factor-alpha (TNF-α) and
TLR-4 have a decreased activity in the combined
regimen (p<0.05) and in the Rego group (p<0.05)
when compared to the control group and correlate withthe histological findings. Likewise, nuclear factor-κB(NF-κB) and IKKα expression decreased in the
combined regimen. Intestinal inflammation assessedby determination of lipopolysaccharide (LPS) is
reduced in the groups where probiotic wasadministered compared to the control and Rego group(p<0.05). In addition, inducible nitric oxide synthaseactivity determined from the intestine diminishes inRego and Rego associated with the probiotic group.
Conclusion: The administration of the Streptococcus
rhamnosus probiotic with Regorafenib improves theantitumoral activity of the multikinase inhibitor. Tumoral
resistance and systemic adverse effects might bediminished when systemic and intestinal inflammation
is lowered. Our results confirmed that the associationof Regorafenib with probiotic proves a novel andpromising approach. Manipulating and trusting your gut
has never been so facile than in the present day for the
oncology field.

(1) Department of Physiology, Iuliu Hatieganu University of
Medicine and Pharmacy, Cluj-Napoca, Romania

Background: Cardiovascular disease is one of theleading causes of death in diabetes mellitus. Most of
the complications in diabetes are due to increased
serum glucose and increased generation of oxygenderived free radicals, which lead to endothelium
dysfunction. Methods: We examined the effect ofquercetin administration on the endothelial NOdependent relaxation (NO-EDR) in the aorta of thestreptozotocin (STZ)-induced diabetic rats. Methods:
STZ-induced diabetic rats were treated with quercetin(30 mg/kg body weight/day). Relaxation response toacetylcholine (ACh) and sodium nitroprusside (SNP)
was measured in the rat aortic rings at the end of thisstudy. Results: ACh-induced EDR was significantly
decreased in Phenylephrine (PE) pre-contracted aorta
of diabetic rats. Quercetin administration preserved
Ach induced EDR, but did not influence SNP-induced
endothelium-independent relaxation in diabetic rat
aorta. Conclusions: Diabetes induced an endothelium
dysfunction. In vitro functional assessment of aortic
rings showed that quercetin administration restored
aorta endothelial function of the STZ-induced diabetic
rats. This improvement of the aorta endothelial function
may be due to the antioxidant mechanisms.
Keywords: acetylcholine; endothelium; diabetes;
quercetin; aorta

18

O18 Chitosan functionalized magnetic
naopartices: between neural regeneration
after peripheric nerve injury andhepatotoxicity
Nadina Liana Pop (1), Alexandrina Nan (2),Andrada-Elena Urda-Cimpean (3), Adrian
Florea (4), Vlad-Alexandru Toma (5, 6), Remus
Moldovan (1), Nicoleta Decea (1), DanielaRodica Mitrea (1), Remus Orasan (1)(1) Department of Physiology, Faculty of Medicine, Iuliu
Hatieganu University of Medicine and Pharmacy, ClujNapoca, Romania; (2) National Institute for Research andDevelopment of Isotopic and Molecular Technologies, ClujNapoca, Romania; (3) Department of Informatics andBiostatistics, Iuliu Hatieganu University of Medicine andPharmacy Cluj-Napoca, Romania; (4) Department of Cell andMolecular Biology, Iuliu Hatieganu University of Medicine andPharmacy, Cluj-Napoca, Romania; (5) Department of
Molecular Biology and Biotechnologies, Babes-Bolyai
University, Cluj-Napoca, Romania; (6) Institute of BiologicalResearch, Cluj-Napoca, Romania

Chitosan is a natural polysaccharide, hydrophilic, nontoxic, with a good chemical and thermic stability.
Chitosan functionalized magnetic oxide ironnanoparticles (CMNPs) appear to have a reduced
cytotoxicity and chitosan protects and stabilizes themagnetic nanoparticle, making it non-detectable for the
immune system. Our study evaluated the effects of
CMNPs on peripheral nerve injuries’ rehabilitation byusing an in vivo experimental model. CMNPs treatment
was administrated daily, orally, for 21 days to rats
subjected to right sciatic nerve lesion and compared tothe control group (no treatment) by analyzing thesciatic functional index, pain level, body weight, serum
nerve growth factor levels and histology, TEM(transmission electron microscopy) and EDX (EnergyDispersive X-ray Spectroscopy) analysis at different
times during the study. Animals treated with CMNPs
had a statistically significant functional outcome
compared to the control group regarding all studied
parameters. In the study we also assessed thepotential adverse effects of CMNPs treatment on
animals’ liver. Hepatic histological modifications
observed in the animals that received CMNPs
consisted in significant periportal inflammation, with norelevant modifications regarding oxidative stressparameters and with a tendency of an antioxidant
effect. In conclusion, oral administrated CMNPs in adosage of 2.5mg/kg for 21 days produced peripheral
nerve regeneration, confirmed by histological studies,
TEM and TEM-EDX, which suggest that CMNPs canbe a promising treatment method for peripheral nerve
injuries. Moreover, CMNPs treatment did not generate
hepatic oxidative stress and appeared to had anantioxidant effect on the liver.
Funding: This research was partially funded by Iuliu
Hatieganu University of Medicine and Pharmacy, Cluj
Napoca, Romania, as a research grant for the firstauthor’s PhD thesis.

O19. Celecoxib: a double-edged sword inmetastatic melanoma
Diana-Valentina Tudor (1), Adrian Florea (2),Mihai Cenariu (3), Gabriela Adriana Filip (1)Affiliations: (1) Department of Physiology, Faculty of Medicine,“Iuliu Hațieganu” University of Medicine and Pharmacy”, ClujNapoca, Romania; (2) Department of Cell and Molecular
Biology, Faculty of Medicine, “Iuliu Hațieganu” University of
Medicine and Pharmacy”, Cluj-Napoca, Romania; (3)Department of Pathology University of Agricultural Sciences
and Veterinary Medicine, Cluj-Napoca, Romania
Introduction: Emerging therapies are changing melanoma
approach. Targeting inflammation markers using celecoxib
seemed a valuable strategy in preclinical studies. Thus, we
assessed for the first time how celecoxib impacts on thephenotype switching phenomenon in metastatic melanoma
cells treated with dabrafenib. Methods: The in vitro
experiments used BRAF positive SK-MEL-28 humanmelanoma cell line, treated with dabrafenib and celecoxib
drug combination, for 72 h. Of main interest was the WB
evaluation of key molecules expressed during theproliferative-invasive phenotype switch (TGF – β, MITF, YAP,
TAZ, AXL). Results were correlated with cell death andoxidative stress-related mechanisms. Results: On one hand,celecoxib increased the apoptotic effect of dabrafenib
compared to dabrafenib single agent therapy (p<0.0001). On
the other hand, celecoxib decreased MITF expression andincreased AXL levels (p<0.0001). Celecoxib and dabrafenib
therapeutic combination increased oxidative stress comparedto the dabrafenib group (p < 0.0001). Conclusion: Celecoxib
might promote MITFlow/AXLhigh expression in SK-MEL-28
cutaneous melanoma, a suggestive hallmark for an invasive
state. This finding could limit its use in future clinical trials.
Further assessment of celecoxib in melanoma is warranted.
Keywords: melanoma, celecoxib, dabrafenib, MITF, AXL.

19

O20. Assessing the safety profile of a drug an itinerary from heart to brain

O21. Infrared laser effects on excitability ofprimary sensory neurons and gating of Nav1.5
ion channels

Beatrice M. Radu, Bogdan Amuzescu
Department of Anatomy, Animal Physiology and Biophysics,
Faculty of Biology, University of Bucharest, Bucharest,
Romania

Drug safety is an essential concept in medical practice.
Pharmacological safety regulations are permanently
improved for both ‚old’ classical and newly-approved
drugs. In accordance with these continuously adapted
regulations it is mandatory to evaluate the proarrhythmogenic risk for each drug. In this respect,according to the Comprehensive in vitro Proarrhythmia
Assay (CiPA) paradigm there are several
proarrhythmogenic risk predictors that can beassessed based on patchclamp recordings of humancardiac channels activity. Another important aspect isthe ability of a drug to penetrate the blood brain barrier(BBB), whether or not it is psychoactive. Moreover, forbrain active drugs it is highly relevant to evaluate theircapacity to activate drug-resistance mechanisms. To
this purpose, our project is widespread approach fromheart to brain that assesses drug safety by in vitro
methods on human induced pluripotent stem cellderived cardiomyocytes or BBB cells, and HEK293T
cells stably or transiently transfected with human ion
channels. Methods include manual and automatedpatch-clamp recordings, mathematical computing,immunofluorescence, transendothelial electricalresistance measurements, Western blot and qRTPCR. So far, we analyzed the drug safety profiles ofseveral drugs belonging to different pharmacologicalclasses in terms of proarrhythmogenic risk predictors
and we are further extending our study to theirinteractions with BBB. In conclusion, pharmacologicalsafety regulations are constantly improved and ourstudy brings relevant informations that can be further
exploited to obtain rapid, reproducible and patientpersonalized drug safety profiles.
B.M. Radu and B. Amuzescu are the owners of theEP18465611.4A/23.12.2020 patent.
Funding: This study was funded from CompetitivenessOperational Programme 2014–2020 project P_37_675(contract no. 146/2016), Priority Axis 1, Action 1.1.4,
co-financed by the European Funds for Regional
Development and Romanian Government funds andby the Romanian Executive Agency for Higher
Education, Research, Development and Innovation
Funding, grant PN-III-P4-PCE-2021-1422.

Bogdan Amuzescu; Florian Armăşescu; Mihai
Ghenghea; Roxana-Olimpia Gheorghe; Dan FlorinMihăilescu
Dept. Biophysics & Physiology, Faculty of Biology, Universityof Bucharest, Romania

Photobiomodulation is a relatively new therapy thathave been proved effective in several
neurological/psychiatric disorders such as stroke, brain
trauma, depression, dementia, and particularly
Parkinson’s disease. Clinical trials provided positiveand encouraging results using either transcutaneous or
deep invasive application of near-infrared laser light,
although the complex cellular and molecular underlying
mechanisms are far from being completely understood.
Therefore we performed a series of manual whole-cellpatch-clamp experiments on dissociated rat primarysensory neurons (ruptured or gramicidin-perforated
approach) and HEK293T cells stably transfected withhNav1.5 voltage-gated Na+ channels. In each setting aseries of voltage/current-clamp protocols was applied
initially and after 3 min since start of exposure to a808.5 nm solid-state laser radiation guided through amultimodal optical fiber connected to a transparent tip
micropositioned above the cell. In neurons laser
exposure produced over the 3-min interval slight
resting potential depolarization and an increase inexcitability (lowered stimulus current threshold andincreased number of action potentials at highest
stimulus amplitude using a multistep current injection
protocol up to 500pA 100ms). In hNav1.5-expressing
cells laser exposure kept unchanged the peak Na+
current amplitude (101.4%±16.7% relative to initialvalues, mean±SEM, n=10 vs. 70.6%±10.4%, n=10
control experiments), slow (103.3%±4.5% vs.
130.7%±17.8% control) and fast inactivation time
constants (105.3%±6.0% vs. 131.2%±11.4% control).
Laser exposure induced no significant changes relative
to control in activation time constant, halfactivation/half-inactivation potential, but decreased theslow time constant of recovery from inactivation to86.3%±16.3%, while in control the fast recovery time
constant increased to 153.5%±14.1%.

20

O22. The antimalarial artemisinin is anagonist of the Transient Receptor Potential
Ankyrin type 1 receptor-channel

O23. Switch of macrophages to M2
phenotype after cytoskeleton alteration
reduces SNL induced neuropathic pain

Debora-Elena Huțanu (1); Alexandra Manolache (1);
George Opriţă (1); Dan Domocoş (1); Teodora
Stratulat (1,4); Susanne K. Sauer (3); Sorin Tunaru(4); Alexandru Babeș (1); Ramona-Mădălina Babeș
(2)

Roxana-Olimpia Gheorghe (1), Andreea Grosu (1),Sorina Dinescu (2), Gisela Gaina (2), Mihail
Ghenghea (1), Damir Sapunar (3), Violeta Ristoiu (1)(1) Department of Anatomy, Physiology and Biophysics,
Faculty of Biology, University of Bucharest, Bucharest,
Romania; (2) Department of Biophysics, “Carol Davila”
University of Medicine and Pharmacy, Bucharest, Romania;(3) Institute of Physiology and Experimental Pathophysiology,
Friedrich-Alexander University of Erlangen-Nuremberg,
Erlangen, Germany; (4) Institute of Biochemistry of the
Romanian Academy, Bucharest, Romania

Introduction. Artemisinin and its derivatives comprisethe most important class of drugs used in medical
practice to treat malaria. When administered, it has
been found that moderate side effects may occur, suchas dizziness, nausea or vomiting. Based on these
considerations, we investigated the possible effects ofartemisinin on three ion channels: TRPM8, TRPV1 andTRPA1.MethodsNon-ratiometric calcium
microfluorimetry experiments were performed on
HEK293T cells, transiently transfected with human
TRPA1, human TRPM8 or human TRPV1, as well as
primary sensory neurons from adult mice. For patch
clamp recordings, HEK293T cells transiently
transfected with hTRPA1 and GFP were plated on 35mm treated Petri dishes and used within 24 hours.
Calcium assay on FlexStation3 was performed on
HEK293T cells transiently transfected with hTRPA1
and G5A.ResultsApplication of artemisinin induced an
influx of Ca2+ into hTRPA1-HEK293T cells and the
response was reversibly inhibited by the specific
TRPA1 antagonist A967079. When artemisinin wasapplied in calcium-free conditions, the response wasreversibly suppressed, resulting that the source of
calcium is extracellular. Artemisinin acts as a nonelectrophilic TRPA1 agonist, activating the channel in asimilar manner to carvacrol. Artemisinin activates
whole-cell currents in HEK293T-hTRPA1 cells
mediated by TRPA1 channels and it activates a
subpopulation of mouse dorsal root ganglion neurons
which also respond to the TRPA1 agonist AITC.
Conclusion: Based on our data obtained onheterologous expression systems and on primarysensory neurons from adult mice, we conclude that
artemisinin acts as a TRPA1 agonist, which could
explain the side effects of the drug.
Funding: This work was supported by a grant of the
Romanian Ministry of Education and Research,
CCCDIUEFISCDI, project number PN-III-P2-2.1-PED2019-5179, within PNCDI III.

Affiliations: (1) Department of Anatomy, Animal Physiology
and Biophysics, Faculty of Biology, University of Bucharest,
91-95 Splaiul Independentei, district 5, 050095, Bucharest,
Romania; (2) Department of Biochemistry and Molecular
Biology, Faculty of Biology, University of Bucharest, 91-95
Splaiul Independentei, district 5, 050095, Bucharest,
Romania; (3) Department of Anatomy, Histology andEmbryology, University of Split School of Medicine, Šoltanska
2, 21000, Split, Croatia

Traumatic nerve injury such as SNL (spinal nerve
ligations) is accompanied by clustering of Iba1 (+)
macrophages around DRG (dorsal root ganglia)
neurons, presumably activating them and facilitatingneuropathic pain development. Previously we haveshown that intra-ganglionic L5 injection of naked siRNA
directed against Iba1 significantly inhibited spinal nerve
ligation-induced mechanical and cold allodynia, 5 days
after the lesion. In this study we investigated whether
the siRNA-induced analgesia is due to a switch in theactivation phenotype of macrophages from M1 proinflammatory to M2 anti-inflammatory accompanied bya reduced mobility of macrophages, andcomplemented by a pro-regenerative profile of DRG
neurons with reduced excitability. The results haveshown that the analgesic effect of Iba1 silencing in
DRG macrophages is due to their functional switch
towards an M2, antiinflammatory state accompanied byan increased secretion of anti-inflammatory cytokinesand pro-regenerative mediators which, however,doesn’t seem to alter significantly theelectrophysiological properties of L5 DRG neurons.
This data are in line with a reduced contribution of L5
DRG neurons to pain pathogenesis after SNL, andsuggest an extended influence of the immune
mechanism to neighboring nonlesioned DRG neurons,possibly responsible for the Iba1 siRNA-induced
analgesia.
Funding: This research was funded by Executive
Agency for Higher Education, Research, Development
and Innovation Funding (UEFISCDI), grant number PNIII-P2-2.1-PED-2019-3103.

O24. TRPM8-dependent “wet dog shake”
behaviour in mammals and birds
Authors: Tudor Selescu
Department of Anatomy, Animal Physiology and Biophysics

Funding: CNCS/UEFISCDI through grant PN-lll-Pl-l.lTE-202 l-1354

21

O25. The Impact of Acute Sepsis on Amyloid
Formation in a Mouse Model of Alzheimer’sAlexandra Daniela Rotaru-Zavaleanu (1,2),
Alexandru Ionuț Neacșu (2,3), Adela-Daria Neacșu
(2), Daniel Nicolae Pirici (4), Eugen Osiac (2,3),
Bogdan Cătălin (2,5)(1) Department of Gastroenterology, University of Medicine
and Pharmacy of Craiova, Romania, (2) Experimental
Research Center for Normal and Pathological Aging,
University of Medicine and Pharmacy of Craiova, Romania,(3) Department of Biophysics, University of Medicine andPharmacy of Craiova, Romania, (4) Department of Histology,
University of Medicine and Pharmacy of Craiova, Romania,(5) Department of Physiology, University of Medicine andPharmacy of Craiova, Romania

O26. The impact of general anesthesia on thedeveloping brain previously exposed toperinatal asphyxia
Sebastian Isac (1,2,); Maria Dobre (3); Elena
Milanesi (3); Artsiom Klimko (4); Irina-Mihaela
Matache (1); Raul-Mihai Paun (1); Mara Ioana
Iesanu (1); Ana-Maria Zagrean (1)(1) Department of Physiology, Faculty of Medicine, Carol
Davila University of Medicine and Pharmacy, Bucharest,
Romania; (2) Department of Anesthesiology and Intensive
Care I, ‘Fundeni’ Clinical Institute, Bucharest, Romania; (3)Victor Babes National Institute of Pathology, Bucharest,
Romania; (4) Department of Neurology, University Hospital
Zurich, Zürich, Switzerland

Funding: This research was funded by the Romanian
Minister of Education, Project No. PN-III-P1-1.2-PD2019-1219

O27. The Impact of Gestational Gut
Microbiome Alteration on
Neurodevelopment in Rat Offspring exposed
to Perinatal Asphyxia
Mara Ioana Iesanu (1,2), Denise Carmen Zahiu (1),
Ioana Alexandra Dogaru (1), Didina Barbalata (1),
Cristian Ciotei (1), Tasnim Chazli (1), Mara Belcin(1), Siobhain M O’Mahony (3,4), Ana-Maria Zagrean(1)(1) Department of Physiology, Faculty of Medicine, Carol
Davila University of Medicine and Pharmacy, Bucharest,
Romania; (2) Department of Pediatrics, Marie Curie
Emergency Children’s Hospital, Bucharest, Romania; (3)Department of Anatomy and Neuroscience, University
College Cork, Cork, Ireland; (4) APC Microbiome Ireland,
University College Cork, Cork, Ireland

O28. Dopaminergic modulation ofhippocampal synaptic plasticity and spatial
memoryVioleta M. Caragea (1,2); Denise Manahan-Vaughan(2)(1) International Graduate School of Neuroscience, RuhrUniversity Bochum, Bochum, Germany; (2) Department of
Neurophysiology, Medical Faculty, Ruhr-University Bochum,
Bochum, Germany

Dopamine is a well-known modulator of cognitive
functions, playing an important role in hippocampal
information processing through means of synaptic
plasticity. In this respect, dopamine acts on two familiesof receptors: the D1-like receptors (D1 and D5) positively coupled to adenylyl cyclase (AC) and the D2like receptors (D2, D3, and D4) - negatively coupled to
AC. On one hand, D1-like receptors seem to play animportant role in regulating the duration and stability ofhippocampal synaptic plasticity for multiple synapses,
as reported by numerous studies from our laboratory.
On the other hand, the role of the D2-like receptors(D2R) in regulating hippocampal synaptic plasticity isless understood and controversial. Recently, we
explored the influence of D2R blockade on synaptic
plasticity at Schaffer collateral - CA1 synapses and on
spatial memory in freely moving rats. Here, we showthat intracerebral pharmacological antagonism of D2R
prevented the in vivo expression of both short-term andlong-term potentiation, as well as the expression ofshort-term depression at CA1 synapses. The same
dose of D2R antagonist also altered the retention of asemantic-like spatial memory task and significantly
impaired retention of recent spatio-temporal aspects ofan episodic-like memory task. Taken together, thesefindings indicate that the D2-like receptors
bidirectionally modulate synaptic plasticity in the
hippocampal CA1 region and play an important role inenabling cumulative and episodic-like forms of spatial
memory.
Funding: This work was funded by the Deutsche
Forschungsgemeinschaft (SFB 874/B10, project
number: 122679504).

22

O29. MR spectroscopy of GABA andglutathione: advancements in dataacquisition, preprocessing and analysis

O30. The information paradigm inNeuroscience

Diana G. Rotaru (1,2,3); Georg Oeltzschner (4,5);
Richard A.E. Edden (4,5); David J. Lythgoe (2)Gabriel Crumpei (1); Alina Gavrilut (2); Lucian Eva(3)(1) Psychology, University of Cambridge, Cambridge, United
Kingdom, (2) Neuroimaging, King’s College London, London,
United Kingdom, (3) National Center for Brain Research,
Research Institute for Artificial Intelligence, RomanianAcademy, Bucharest, Romania, (4) Russell H. Morgan
Department of Radiology and Radiological Science, The
Johns Hopkins University School of Medicine, Baltimore, MD,
United States, (5) F. M. Kirby Research Center for Functional
Brain Imaging, Kennedy Krieger Institute, Baltimore, MD,
United States(1) Department of Psychology, Faculty of Psychology and
Educational Sciences, Alexandru Ioan Cuza University, Iasi,
Romania; (2) Department of Mathematics, Faculty ofMathematics, Alexandru Ioan Cuza University, Iasi, Romania;(3) Department of Dental Medicine, Apollonia University, Iasi,
Romania

Until recently, neuro-metabolites like the main
inhibitory neurotransmitter, GammaAminobutyric Acid
(GABA) and the antioxidant found throughout thebrain, glutathione (GSH)) were unresolvable using
standard Magnetic Resonance Spectroscopy (MRS)
techniques due to their low concentrations and weakMR signals. Based on recent work on data acquisition
schemes, discrimination and quantification of GABA
and GSH became possible. However, improving theacquisition solely is not enough as despite the highquality GABA results, GSH still suffers from poor
spectral discrimination that translates into poorer
concentration estimates. We propose a new analysis
approach for the simultaneous assessment of GABA
and GSH spectra: Concatenation Of Hadamard
Encoded and Reconstructed spectra of Edited
NeuroChemicals Estimates (COHERENCE). Our novel
analysis pipeline was successfully implemented for
simultaneous modeling of GABA and GSH HERMES
data. While GABA results were similar to those of the
traditional GABA difference single-spectrum analysis,
for GSH, COHERENCE has shown a better agreement
between scanning sessions. The repeatability of
COHERENCE was comparable to traditional
singlespectrum modeling.

.

Nowadays, information is a notion present everyday,
both in common language and in research andscientific works. Trying to define information is difficult
because it is present at all levels of reality, from thequantum level to the cosmic one, and the definitions so
far capture only certain aspects of what we callinformation. A coherent theory of information wasdeveloped by Shannon and Weaver over 70 years ago,
but this is rather a theory of communication inelectronic systems. Information technology andresearch in robotics and artificial intelligenceincreasingly highlight the need to define and integrate
information in theories related to physical and biologicalreality. There are some attempts in neuroscience tobuild physical-mathematical models of reality, which
include information. We have some theories developedin the last part of the 20th century and the beginning of
the 21st century related to fractal geometry, topology,
complex systems theory and network science, which
are used in this offensive to define and integrate
information in our theories about the world and life. The
evolution in these fields is strictly linked to establishing
the role of information, along with matter and energy, inthe construction of reality. It is necessary to determine
if information has a fundamental character in nature, if
it is a ubiquitous universal aspect of reality and what
are the relationships between substance, energy andinformation, starting from the immaterial nature of
information.

23

ABSTRACT - POSTER PRESENTATIONSPOSTERS WITH BLITZ ORAL PRESENTATIONS
B01. Alteration of sleep stages in a murine
model of temporal lobe epilepsy

B02. Assessment of the rat ischemic brain by
burst-suppression EEG reactivityȘtefan-Alexandru Țîrlea (1), Vlad-Petru Morozan(1), Mihai Stancu (2), Diana-Andreea Ilie (1), AndreiVladimir Iacovache (1), Ana-Maria Mațotă (1),Bianca-Ioana Guțu (1), Armand Nicolicioiu (3),Carmen-Denise-Mihaela Zahiu (1), Ana-MariaZăgrean (1)Andrei Bordeianu (1); Alexandru Pâslaru (1);
Laurențiu Tofan (1); Mihai Stancu (1,2); Bogdan
Pavel (1); Carmen-Denise Zahiu (1); Andrei Ilie (3);Alexandru Călin (4); Ana-Maria Zăgrean (1); LeonZăgrean (1); Mihai Moldovan (1,5,6)(1) Department of Functional Studies, Division of Physiology,
Center for Excellence in Neuroscience, University of Medicine
and Pharmacy Carol Davila, Bucharest, Romania; (2)Department Biology II, Division of Neurobiology, LudwigMaximilians-Universität, München, Germany; (3) Faculty ofMathematics and Computer Science, University of Bucharest,
Bucharest, Romania

Epilepsy is a common condition that affects the brain
causing multiple seizures. The disease is diagnosed bycorrelation of the clinical manifestation with thehypersynchronous wave on EEG known as epileptic
spike. However, epileptic spike capture is inconsistentin the early stages, thus increasing the need for further
research. This study aims to validate an alteration of
the sleep stages in a temporal lobe epilepsy murine
model, as a hypothetical approach for epilepsy early
diagnosis methods. We induced epilepsy in C57Bl/6
mice using kainic acid administration in the
hippocampus. Concurrently, we surgically implanted aheadstage to the experimental lot (n=3) and control(n=2). The mice were ECoG, EMG (4+1 channels)
recorded and video tracked for 24 hours. Data wassplit in 30-second epochs and plotted into raw ECoG
tracings and power spectrum. The epochs wereclassified by sleep stage and epileptic activity using
both visual inspection and entrainment of a machinelearning model. The data revealed an increased timespent in wake, during which most epileptic spikes were
captured. Furthermore, the sleep fragmentation was
reduced in the epileptic mice, compared to control,suggesting a similar mechanism of the epileptic spikes
and K-complexes in maintaining the sleep stage.
Although the results are preliminary, the alteration of
circadian rhythm and decrease in sleep fragmentation
could be linked to temporal lobe epilepsy and might
facilitate further diagnostic methods.

(1) Department of Functional Sciences, Center for Excellence in
Neuroscience, Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania; (2) Biology, Ludwig-MaximiliansUniversity of
Munich, Munchen, Germany; (3) Neurology, Royal Victoria Infirmary,
University of Newcastle, Newcastle, United Kingdom; (4) Neurology,
University of Newcastle, Newcastle, United Kingdom; (5)Neuroscience, University of Copenhagen, Copenhagen, Denmark; (6)Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark

Aim: The electroencephalographic (EEG) assessmentof the diffuse ischemic brain injury remains
methodologically challenging. The aim of this study
was to investigate the impairment in EEG reactivity tointermittent photic stimulation (IPS) following
experimental global cerebral ischemia. Rather thanfocusing on continuous EEG measures, we tested thereactivity of the discontinuous burst-suppression (BS)patterns induced in deep anesthetic coma. Methods:
Male Wistar rats were surgically exposed to a mild
global cerebral ischemia by electrocauterization of thevertebral arteries and the subsequent clamping of bothcommon carotid arteries for 5 minutes under laser
doppler control. A group of rats exposed to shamsurgery served as controls. Cortical EEG recordings
were carried out at 48 hours after surgery when all rats
appeared clinically recovered. The BS patterns,
induced by an overdose of Chloral hydrate, were
quantified by the suppression ratio (SR), measuring thefraction of time spent in suppression, over 1-minuteintervals. The IPS was delivered to one eye at 0.5 Hz in
1-minute epochs. The BS reactivity index (BSRI) was
defined as the reduction in the ipsilateral SR that
occurred during IPS, relative to the baseline SR
recorded just prior to IPS. Results: At a baseline SR of
40%-80%, the mean BSRI was 0.27 seconds. In
contrast, the mean BSRI was about 3-fold smaller inthe rats exposed to GCI. The amplitude of the visualevoked potentials was similar between the groups.
Conclusion: Our data suggest that measures of the
burst-suppression EEG reactivity are sensitive to detect
the post-ischemic brain injury.
The work with Termobit Prod SRL RO is protectedunder patent EP3646784B1 Funding: This project was
supported by grants of the Romanian National
Fiziologia - Physiology • 2022. SUPPLEMENT 1

24

Authority for Scientific Research, CNCS – UEFISCDI,
project number PN-II-ID-PCE-2011-3-0847, PN-II-PTPCCA-2011-3.2-1290 and PN-III-P2-2.1PTE-20160114 to Mihai Moldovan.

B03. Burst-suppression EEG reactivity in a
genetic model of absence epilepsy
Ana-Maria Matota (1); Alexandru Catalin Paslaru(1); Mihai Stancu (1,2); Laurentiu Tofan (1);
Dorottya Szocs (1); Bogdan Pavel (1); Ana-Maria
Zagrean (1); Leon Zagrean (1); Mihai Moldovan(1,3,4)(1) Department of Functional Sciences, Center for Excellencein Neuroscience, Carol Davila University of Medicine andPharmacy, Bucharest, Romania; (2) Biology, LudwigMaximilian University of Munich, Munich, Germany; (3)Neuroscience, University of Copenhagen, Copenhagen,Denmark; (4) Clinical Neurophysiology, Rigshospitalet,
Copenhagen, Denmark

Aim: The burst-suppression (BS) patterns emerging on
the electroencephalogram (EEG) in deep anestheticcoma are reactive to external stimulation. We aimed toinvestigate whether this BS reactivity is increased in
the epileptic brain. Methods: Acute experiments werecarried out in adult Wistar Albino Glaxo Rijswijk(WAG/Rij) rats, a commonly used genetic model ofabsence epilepsy which presents characteristic
episodes of spike-and-wave discharges (SWD) lasting
about 6 seconds on the wake EEG. Age-matched
Wistar rats served as control. Cortical EEG recordings
were carried out during isoflurane anesthesia. The BS
patterns were quantified by the suppression ratio (SR),measuring the fraction of time spent in suppression,over 1-minute intervals. Investigations were carried out
at a baseline SR of 40% – 80%. Intermittent photic
stimulation (IPS) was delivered to one eye at 0.5 Hz in
1-minute epochs. Given the predominantly crossed
visual pathways, the SR was assessed ipsilaterally tominimize the confounding effect of the visual evoked
potentials. A BS reactivity index (BSRI) was defined as
the reduction in SR that occurred during IPS, relative
to the baseline SR recorded just prior to IPS.Results:
The IPS under deep anesthesia did not trigger SWDs.
The mean BSRI was 0.2 in controls. In WAG/Rij themean BSRI was increased by 55%. The difference was
reduced after ethosuximide and paradoxicallyincreased after carbamazepine at doses that had noeffect on controls.Conclusion: Our data suggest thatmeasures of burst-suppression EEG reactivity could be
useful to assess the hyperexcitability of the epileptic
brain.
The work with Termobit Prod SRL RO is protectedunder patent EP3646784B1
Funding: This project was supported by grants of the
Romanian National Authority for Scientific Research,
CNCS – UEFISCDI, project number PN-II-ID-PCE2011-3-0847, PN-II-PT-PCCA-2011-3.2-1290 and PNIII-P2-2.1PTE-2016-0114 to Mihai Moldovan

B04. EFFECT OF LONG TERM If CURRENTBLOCKADE ON THE OCCURANCE OF
SPONTANEOUS ATRIAL FIBRILLATIONEPISODES FOLLOWINGTRANSESOPHAGEAL ATRIAL BURSTPACING
Vasile Bogdan Halațiu (1); Alkora Ioana Balan(1,2); Dan Alexandru Cozac (1); Cosmin
Constantin Mutu (1); Emilian Comșulea (1);Marcel Perian (1); Alina Scridon (1,2);(1) Physiology Department, “George Emil Palade” Universityof Medicine, Pharmacy, Science and Technology, TârguMureș, Romania; (2) Center for Advanced Medical andPharmaceutical Research, Târgu Mureș, Romania;

Introduction: Data in the literature regarding the effectsof ivabradine, a selective inhibitor of the funny current,
on atrial arrhythmogenicity are controversial. Thus, weaimed to assess the effect of pacemaker current
blockade the occurrence of spontaneous episodes ofatrial fibrillation (AF) following transesophageal atrial
burst pacing in rats. Material and Methods: A total of 32
male Wistar rats were randomly assigned into twogroups: FA (n = 16) and IVA (n = 16), the latterreceiving Ivabradine (10 mg/kg/day) in the drinking
water for three weeks prior to and throughout the study.
All animals were implanted with radio-telemetry ECG
devices and the ECG was recorded for 72-h before,
during and one week after transesophageal atrial burst
pacing. Transesophageal atrial burst pacing wasapplied for 10 days to the rats in both groups. Results:
The baseline heart rate was significantly lower in the
IVA compared with the FA group (302± 40,25 vs. 351±
38,40 bpm, p< 0.001). In the absence of electricalstimulation, rats in the IVA group presented a higher
number of AF episodes per 24 hours (p< 0.01)
compared to the rats in the FA group. A higher numberof AF episodes was also observed after the initiation of
the protocol (p< 0.01), as well as one week after its
completion (p = 0.02). Conclusions: Our results
demonstrate an important in vivo proarrhythmic effectof ivabradine, expressed as an increased number of
spontaneous AF episodes. The exact mechanism
through which ivabradine increases AF susceptibility
needs further investigations.

25

B05. Electrocorticographic changes induced
by deep brain stimulation under anaesthesia
in rats

B06. Identification of corticotropin releasing
hormone projections to the thalamic reticular
nucleusPatricia-Demetria Popovici (1), Denise Zahiu(1), Diana Ilie (1), Madalina Gherghe(1), Alexandru-Catalin Paslaru (1), Daniela Iliescu(1), Diana Rotaru (2), Ana-Maria Zagrean(1), Bogdan Pavel (1)Oprita George (1), Cumpana Loredana (2)Division of Physiology and Neuroscience, Carol Davila
University of Medicine and Pharmacy, Bucharest, Romania;(2) Department of Neuroimaging, Centre for Neuroimaging
Sciences, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, London, UK

General anaesthesia is induced for thousands ofprocedures annually, but the exact mechanism ofgeneral anaesthetics is not completely understood.
The claustrum is a cerebral structure that, despite its
reduced dimensions, has the highest number ofconnections/volume and it is considered to play a rolein the state of consciousness. The aim of this study
was to investigate the effects of claustrum electricalstimulation on the anaesthesia depth during ketaminexylazine anaesthesia in adult rats. In this study, weused ten adult rats. Anaesthesia was induced with aketamine-xylazine cocktail. Three electrocorticogram
electrodes were placed on the left frontal and parietal
lobe and right olfactory cortex. A bipolar tungsten
electrode was inserted into the left claustrum. The
claustrum was electrically stimulated by applying 10
stimuli of 1 second duration each, at interstimulusinterval of 5 seconds. Five-second-epochs wereselected in the basal period and corresponding to thefirst three applied stimuli and to the first threeinterstimuli time intervals. ECoG analysis using frontoparietal connectivity and median frequency were
performed in order to assess the anesthesia depthchanges. The results were compared using ANOVA
one-way with Dunnet T3 correction. Our results
revealed that there were no statistically significant
differences in fronto-parietal connectivity (p= 0.835),
parietal median frequency (p=0.265) or frontal medianfrequency (p=0.262) between the basal period, thestimulation period and the period between thestimuli.In conclusion, in this study, we have shown thatelectrical stimulation of claustrum under ketaminexylazine anaesthesia induces no changes in the depthof anaesthesia.

(1) Department of Anatomy, Animal Physiology andBiophysics, Faculty of Biology, University of Bucharest,
Bucharest, Romania; (2) School of Life Sciences, École
polytechnique fédérale de Lausanne, Lausanne, Switzerland

The thalamic reticular nucleus (TRN) is comprised of
GABAergic neurons that ensheathe the thalamus, while
receiving collaterals from both thalamic and corticalneurons. Its functions include sensory integration andvarious modulations of attention, while disfunctions of
this area have been associated with afflictions like
autism and schizophrenia. The corticotropin releasing
hormone (CRH) is mainly associated with its function
as the first signaling molecule of the hypothalamuspituitary-adrenal (HPA) axis and the neuroendocrine
response to stressful stimuli. CRH also acts as aneuromodulator in the central nervous system, where it
influences behaviors related to anxiety and stress,
independent of the HPA axis. Even though TRN ischaracterized by a high expression level of the CRH
receptor 1, the link between CRH and this brain area
was not thoroughly investigated. Using transgenic mice
which express the Cre recombinase in cells that
express CRH and confocal imaging on brain slices, thisstudy identified brain regions that send CRH
projections to the TRN. Retrograde labelling using viral
vectors identified several candidate regions whose
projections may release CRH in the TRN, these being
the basolateral amygdala, the suprageniculate nucleus,
the ventral lateral geniculate nucleus and the medial
geniculate nucleus. The medial geniculate nucleus andthe suprageniculate nucleus projections have been
confirmed with anterograde labelling. Further studies
could search for more potential projecting areas,
confirm the ones found with retrograde labelling orinvestigate the functional or behavioral alteration of
CRH signaling in the TRN.
Funding: This project has received funding from theEuropean Union Horizon2020 Research and Innovation
programme under the Marie Sklodowska-Curie grant
agreement No. 813986.

26

B07. Invasive presurgical exploration ofvisual system epilepsy
Tofan Laurentiu (1,2), Felicia Mihai (3), Irina Oane(2), Andrei Barborica (3), Ioana Mindruta (1,2)(1) Faculty of Medicine, UMF “Carol Davila”, Bucharest,
Romania; (2) Neurology, Universitary Hospital of Bucharest,
Bucharest, Romania; (3) Physics Department, University of
Bucharest, Bucharest, Romania

Epilepsy represents one of the most common
neurological chronic diseases worldwide affecting over
50 million people. Although there has been madeimportant progress regarding the pharmacologicalapproach for this disease, over 20% of these pacients
have a pharmaco-rezistant form of epilepsy. In thiscase, the surgical method represents an alternative.
We have investigated patients included in the National
Pharmacoresistant Epilepsy Programme, hospitalised
at the University Hospital in Bucharest. We haveanalyzed their response when stimulated with electric
current provided by intracerebral electrodes andfocused on the visual phenomenons, in particular, thevisual hallucinations. We have looked at the localisationof the stimulating electrode, the intensity of the electric
current, the clinical effect, the color of the hallucinationand the initial and final localisation of this visual
phenomenon. We have observed a higher number of
hallucinations than illusions. Most patients experienced
simple hallucinations with “positive” simptomatology.
The continuous hallucinations were more frequent than
the intermitent ones. When taking into consideration
the initial and last position of the hallucination in thevisual field, the “static” hallucinations were morecommon than the “dynamic” ones. The visual elementsthat have been experienced by the patients werepredominantly characterised as “non-color”. In terms of
secondary symptomatology associated with visual
hallucinations, the patients mainly experienced visual
illusions.

B08. The impact of general anaesthesia on thedeveloping brain previously exposed toperinatal asphyxia
Irina Mihaela Matache1, Sebastian Isac1, Artsiom
Klimko1,2, Raul Paun1, Ana Teiusianu1, Eugen
Tanase1, Ana-Maria Zagrean1
1-Carol Davila University of Medicine and Pharmacy, Center for
Excellence inNeuroscience, Department of Functional
Sciences, Bucharest, Romania,
2-University Hospital Zürich, Laboratory of Molecular NeuroOncology, Department of Neurology, Zürich, Switzerland

Aims: General anaesthesia (A) in paediatric patients is
extensively used nowadays, although it still represents
a debatable concern, especially in the context of its cooccurrence with other clinical conditions, such asperinatal asphyxia (PA). Our experimental study
investigates hippocampal glial activation andinflammation secondary to PA or A alone, and tocombined exposure (PAA).
Methods: On postnatal day (PND) 6, we exposed Wistar
rats to 90-minute of either asphyxia (PA) or normoxia,
and on PND-15 to 180-minute of either sevoflurane
anaesthesia (A) or normoxia. Hippocampal tissue wasimmediately harvested thereafter from each of the 4groups (control, PA, A, PAA; 15 animals/group), and S100B and IL-1B were assessed by ELISA.
Results: Our results revealed an increased hippocampal
level of S-100B consecutive to PA, A, and combined
PAA exposure, showing that both PA and A significantly
contribute to glial activation, however with no cumulative
effect. The hippocampal level of IL-1B was increased
consecutive to PA, was not impacted by A alone whencompared to control, and was decreased in PAA groupwhen compared to PA group.
Conclusions: Our study pointed out that PA has adeleterious effect on the immature hippocampus byincreasing glial activation and neuroinflammation, while
A alone produces only glial activation. When combined,
PA and A do not potentiate reciprocally. Further studies
are needed to better understand the controversial
general anaesthesia impact in pathophysiologicalconditions like PA, to ultimately increase the patients’safety.
This research was supported by the Romanian Ministerof Education, Project No. PN-III-P1-1.2-PD-2019-1219.

27

B09. siRNA-mediated gene silencing using
magnetofection: different perspectives on
HMC3 microglia maintained in definedmedium
versus standard medium conditions

B10. The dose-dependent effects ofbetacyclodextrin complexed lacosamide on
seizure-like events induced by lowmagnesium in rat hippocampal slices

Melania Bica-Popi (1); Gabriela Chiritoiu (2);
Cristian Munteanu (2); Violeta Ristoiu (1)Rita-Judit Kiss (1), Ágnes Csüdör (1), ÁdámJózsef Berki (2), Károly Orbán-Kis (1), Zsolt
Gáll (3), Tibor Szilágyi (1)(1) Department of Anatomy, Animal Physiology andBiophysics, Faculty of Biology, University of Bucharest,
Romania; (2) Department of Molecular Cell Biology, Instituteof Biochemistry, Romanian Academy, Bucharest, Romania.

Aims: Serum-free microglia culture models
supplemented with primary components of astrocytederived factors (defined-medium) are required for thecells in vitro to recapitulate the mature, resting
microglial phenotype. Here, we characterized theeffects of magnetofection to deliver siRNA in HMC3
microglia cultured in defined medium as well as
standard medium conditions. Methods: The
polarization towards the resting phenotype of HMC3
microglia maintained in defined medium wasestablished by quantifying the degree of cell elongation
across the nucleus. The efficacy of magnetofection, anovel transfection method that delivers nucleic acids
upon exploitation of magnetic force, was assessedusing siRNA molecule labelled with A594. The images
were analyzed quantitatively to establish the optimal
concentration of siRNA and the ideal ratio between
siRNA and the transfection reagent. The efficiency ofmagnetofection was tested using a customized antiIba1 siRNA molecule, by Western blot and LC-MS
analysis. Results: The degree of cell elongation, but
not the cell area, revealed significant morphologicalchanges in HMC3 microglia cultured in definedmedium as compared to HMC3 cells cultured in serumsupplemented media. The dose-response curve ofsiRNA-A594 uptake as well as the ratio between
siRNA-A594 and the transfection reagent indicate amore effective delivery in serum supplemented
cultures as compared to defined-medium conditions.
The Western blot data showed a decrease in Iba1
expression after siRNA anti-Iba1 molecule uptake,even though the results were not striking: surprisingly,
we confronted a low level of Iba1 protein intrinsically
expressed by HMC3 microglia, confirmed by LC-MS
analysis. Conclusion: Culture-dependent differences
are revealed by magnetofection in HMC3 microglia.
Funding: Unitatea Executiva Pentru Finantarea
Invatamantului Superior a Cercetarii Dezvoltarii si
Inovarii: PN-IIIP2-2.1-PED-2019-3103(1) Department of Physiology, Faculty of Medicine, George
Emil Palade University of Medicine, Pharmacy, Science And
Technology of Targu Mures, Targu Mures, Romania, (2)Department of Neurology, Semmelweis University, Budapest,
Hungary, (3) Department of Pharmacology and ClinicalPharmacy, Faculty of Pharmacy, George Emil Palade
University of Medicine, Pharmacy, Science And Technology of
Targu Mures, Targu Mures, Romania

Epilepsy affects around 50 million people worldwide.
Drug-resistant epilepsy is frequent, due, in part, to themolecular properties of the available drugs, such as
poor solubility and bioavailability. There is evidence
that in vitro seizure models can predict the antiepileptic
efficacy of standard antiepileptic drugs. The objectiveof our project was to study the effects of the widelyused beta-cyclodextrin (BCD), as excipient for the
improvement of bioavailability of several drugs. We
also tested the dose-dependent effect of BCDcomplexed lacosamide on seizure-like events (SLE) in
vitro. We removed the brains of rats (P7-12), obtained
400µm thick slices and placed a microelectrode in the
pyramidal layer of CA3 region of the hippocampus torecord field potential. Initially an artificial cerebrospinal
fluid (nACSF) was applied to record the baseline
activity, followed by a seizure-inducing solution(0MgACSF), then 0MgACSF containing BCD eitherwith lacosamide (25µM, 50µM and 100μM) or without
and final washout. We observed that the BCD reduced
the length of interictal periods significantly: 163±13.26(mean±SEM) vs 118±12.08. The BCD and 25 μM
lacosamide combination significantly decreased both
ictal (62.38±3.93 vs 39.18±3.19) and interictal(153.1±8.35 vs 76.72±11.08) periods, so the seizure
frequency was increased, but these were shorter. The
50µM concentration lacosamid reduced the ictal length
further (39.18±3.19 vs 23.23±2.82), but the interictal
period was longer then in 25µM (91.03±9.22), so it
resulted even shorter SLE-s and also a lower seizure
frequency. We conclude that BCD may preserve thedose-dependent inhibitory effect of lacosamide on the
SLE’s that warrants its further investigation.
Funding: This work was supported by the University of
Medicine, Pharmacy, Science and Technology of
Târgu Mureș Research Grant number 615/7,
17.01.2019

28

B11. The effects of Cornus mas L. extract on
cardiovascular modifications in anexperimental diabetes mellitus model
Remus Moldovan (1), Daniela-Rodica Mitrea (1),Irina-Camelia Chiş (1), Luminiţa David (2), Bianca
Elena Moldovan (2), Laura Elena Mureşan (3),Şoimiţa Suciu (1), Simona Clichici (1)(1) Department of Physiology, Iuliu Hatieganu University of
Medicine and Pharmacy, Cluj-Napoca, Romania; (2)Research Center for Advanced Chemical Analysis,
Instrumentation and Chemometrics, Faculty of Chemistry andChemical Engineering, Babes-Bolyai University, Cluj-Napoca,
Romania; (3) Raluca Ripan Institute of Research in
Chemistry, Babes-Bolyai University, Cluj-Napoca, Romania.

Background. Recent research presents natural
extracts as efficient therapies in inflammation,
hyperglycaemia and localized pathological processes.
Several studies showed the efficiency of gold
nanoparticles (AuNPs) in the drug transportation
toward target tissues. Aims. Our study investigated, in
rats with high fat diet and diabetus mellitus, thecardiovascular effects of the oral administration ofCornus mas, a plant rich in antioxidants, when given
as simple extract solution or as a functionalizing agent
for AuNPs. Methods. Adult Sprague Dawley female
rats, with high fat diet for 8 months that increased theirbody weight till 600 ± 20g and streptozocin-induced
diabetes mellitus, were randomly allocated in: CMC
group with carboxymethylcellulose (CMC)
administration; Insulin group with Insulin treatment;
Pioglitazone group treated with pioglitazone in CMC
solution; AuNPsCM group with solution of gold
nanoparticles functionalized with Cornus mas L.
extract (AuNPsCM) and Cornus mas group treatedwith extract of Cornus mas L.solution. The treatment
was administered for one month. The oxidative stressand inflammatory parameters were evaluated in aorta
wall and heart. Results. The administration of Cornus
mas L. extract simple solution recorded significant
modifications: malondialdehyde and TNF-α weredecreased in aorta wall and heart tissue, endothelin-1
was decreased in aorta and GSH/GSSG ratio wasincreased in heart homogenate. AuNPsCM treatment
produced significant effects: TNF-α decreased in aorta
and heart, butiNOS increased in the investigatedtissues. Conclusions. The aorta and heart were
protected by the Cornus mas L. extract simple solution,
presenting decreased oxidative stress andinflammation. AuNPsCM treatment presented
contradictory effects on inflammation, in aorta andheart tissue.

.

B12. The Alteration of Rat Offspring
Neurodevelopmental Reflexes after
Gestational Gut Microbiome Disturbance andPerinatal Asphyxia
Didina Catalina Barbalata (1); Cristian Ciotei (1);Mara Ioana Iesanu (1,2); Ioana Alexandra Dogaru(1); Denise Carmen Zahiu (1); Tasnim Chazli (1);Mara Belcin (1); Ana-Maria Zagrean (1)(1) Department of Physiology, Faculty of Medicine, Carol
Davila University of Medicine and Pharmacy, Bucharest,
Romania; (2) Department of Pediatrics, Marie Curie
Emergency Children's Hospital, Bucharest, Romania

Introduction: Maternal gut microbiota disturbance has
been linked to alterations in the offspring's
neurodevelopment. Perinatal asphyxia (PA) can induce
altering effects on the immature brain. Our study
evaluates the impact of gestational antibiotic
administration (GAA) and PA on offspring’s
neurodevelopmental reflexes.
Material and methods: We conducted GAA on the 11th
gestational day of Wistar rats who were orally
administered a cocktail of antibacterial and antifungal
medication (ampicillin, vancomycin, neomycin,
clindamycin, and amphotericin-B) in the water. Afterbirth, pups were divided into 4 groups: controlnormoxia (C-N), antibiotics-normoxia (AB-N), controlperinatal asphyxia (C-PA) and antibiotics-asphyxia(AB-PA). In the 6th postnatal day (PND), we recorded,with a MouseOx monitor, the vital signs of C-PA and
AB-PA pups exposed to a 90 min-asphyxia (9% O2,
20% CO2 in N2). In 7-9 PND, we exposed the pups tothe following early-life behavioural tests: righting reflex(RR), limbs grasping reflex (LGR), cliff avoidance (CA),negative geotactic reaction (NGR) and grip strength
response (GSR).
Results: GAA has led to a high percentage of
miscarriage and low offspring birth weight. During PA
the oxygen saturation decreased to 45.41%. During
RR, pups in AB-PA group showed prolonged time toright. During LGR, we observed a low average ofsuccessful limb grasps in C-PA and AB-PA groups. In
CA, AB-N and AB-PA groups showed prolonged
turning time. The pups in AB-PA group showed thehighest latency to turn during NGR. The AB-N groupexhibited the weakest paw strength during GSR.
Conclusion: Our preliminary results show that maternal
dysbiosis and PA lead to early-onset brain impairment
and recommend increased caution whenrecommending gestational antimicrobials use.

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POSTERS
P01. A non-inflammatory soft tissue around
implants a key factor for long term success.
Clinical cases.
Adrian Teodor Moga Rogoz
Department of Physiology, Faculty of Medicine, University of
Medicine and Pharmacy, Cluj-Napoca, Romania

It is long proven that where we have inflammation
there is oxidative stress. The same principle is in thecase of dental implants; because between theprosthetic construction and connective tissue(transition zone) that covers the bone next to theimplant in most of the cases, patients present signs ofinflammation (tumor, pain, and change in colorredness). All of this because the connective soft tissue
that surrounds the prosthetic construction in somecases randomly forms a new natural bonding to theprosthesis that similar to the natural Sharpey fibers
and in other cases there is no connection. We knowthat some implantable materials are better than others
in terms of plaque adhesion, bacterial biofilm
formation, and tissue likeness. Another importantcriteria for the long term success of the therapy is thegeneral state of health of the patient. As a inclusion
criteria for the clinical cases followed was that all thepatients to be adults, to have a good state of health,good dental hygiene and proper prosthetic
reconstruction. After implantation and reconstruction,
we did a 6 month and 1 year follow up. During thehealing process we treated our patients with natural
local antioxidants. As result we came up with a rate of
3% of implant lost and 97% rate of survival of theimplant and prosthetic reconstruction. In our opinion
one of the most important is a good healthy and noninflammatory tissue around dental implants. But we stillsuggest for making further clinical studies in thisdirection.

P02. Adiponectin from brain to heart and backRoxana Deac (1), Florina Batar (2), Manuela
Pumnea (3)(1) Department Physiology, Faculty of Medicine, University“Lucian Blaga’ Sibiu, City Sibiu, Country Romania.

P03. Anti-inflammatory nanodrugs for stroke
treatment
Cercel Andreea-Mihaela, Abuzan Mihaela, Burdusel
Daiana, Madalina Aldea, Aurel Popa-Wagner
University of Medicine and Pharmacy of Craiova,
Biochemistry, Neurobiology of Aging Group, Romania

Despite recent progress, the large majority of ischemic
stroke patients still exhibit neurological deficits in thelong run, and ischemic stroke continues to be the mostfrequent cause of long-term disability. Nanosized small
extracellular vesicles (sEVs) prepared frommesenchymal stromal cell (MSC) supernatants havepreviously been shown to promote neurologicalrecovery and brain remodeling in ischemic strokemodels. sEV-based therapies are not self-replicating
and lack endogenous tumor formation potentials andtherefore are rapidly approaching clinical trials inhuman stroke patients. A major challenge of stroke
therapies are vascular risk factors associated withageing (e.g., hyperlipidemia, diabetes mellitus), which
exacerbate inflammatory responses in the brain andcompromise recovery. In previous work we have shownthat MSC-sEVs efficaciously reversed the postischemic responses of polymorphonuclear neutrophils(PMNs), monocytes/macrophages, T cells and B cells
in the peripheral blood and/or brain, indicating towards
an immunomodulatory effect of MSC-sEVs that might
confer their therapeutic activity. The aim of this study
is to (a) comprehensively characterize immune signals
mediating recovery-promoting effects of MSC-sEVs in
the ischemic brain, (b) evaluate consequences of age
and age-associated vascular risk factors (i.e., diabetes,
hyperlipidemia) for post-ischemic immune responses
and the recovery-promoting effects of MSC-sEVs,(c)examine the role of peripheral blood-derived PMNs andmicroglial cells in MSC-sEV-induced neurologicalrecovery, through nanosizing EVs through colloidal
engineering, in depth cell biological characterization, in
vitro and in vivo models, confocal and 2-photon
microscopy, transcriptomics and behavioral analysis.
By providing efficacy data in the aged ischemic brain
exhibiting vascular risk factors, we hope to allow an in
depth estimate of the therapeutic efficacy of MSCderived sEVs in human stroke patients.

Adiponectin is the most abundant specific protein
secreted and expressed by adipocytes. The different
forms of Adiponectin have different biologicalproperties and different tissues targets. To exert its
biological effects, Adiponectin must bind to its specificreceptors: AdipoR1, AdipoR2 and T-cadherin. The
biological actions of Adiponectin are: insulinsensitizing, anti-inflammatory effect, anti-atherogenic
effect, anti-proliferation in cancer, regulation of glucose
and lipid metabolism, neuroprotective effects. In
conclusion, Adiponectin is gaining attention as apotential therapeutic target.
Fiziologia - Physiology • 2022. SUPPLEMENT 1

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P04. Blood pressure effects of SGLT-2
inhibitors treatment in patients with type 2
diabetes mellitus
Cosmin Mihai Vesa (1), Marius Rus (2), DorinaGălușcă (2), Andreea Atena Zaha (3), Dana Carmen
Zaha (1)(1) Preclinical Department, Faculty of Medicine andPharmacy, University of Oradea, Oradea, Romania; (2)Clinical Department, Faculty of Medicine and Pharmacy,
University of Oradea, Oradea, Romania; (3) Faculty of
Medicine, University of Medicine and Pharmacy Iuliu
Hatieganu, Cluj-Napoca, Romania

Introduction. Hypertension is a major cardiovascularrisk factor in type 2 diabetes mellitus patients that
greatly increases the risk for acute cardiovascular
events. The purpose of our study was to evaluate theeffects of blood pressure in a real-life study including
patients with type 2 diabetes mellitus. Material andmethods. 10 patients with type 2 diabetes mellitus
evaluated in a private medical clinic in Oradea,
Romania were included in the study. Their average
age was 57.2 years, 60% were men and 40% women,
their average duration of diabetes mellitus was 4.3
years. All of them were on metformin therapy alone.
Their average HbA1c was 8,19 ± 0.28%, therefore
introduction of another antidiabetic agent wasnecessary. Dapagliflozin 10mg 1 tablet/ day orempagliflozin 25 mg 1 tablet/day were introduced intheir therapy. Blood pressure was measured by
auscultatory method using an automatedsphygmomanometer according to the ESC 2018
guidelines at treatment initiation and after 2 months.
Results. The average systolic blood pressure was
149,6±4,77mmHg while the diastolic blood pressure
was 92,1±2.79mmHG. 7 out of 10 patients weretreated for blood pressure according to the current
guidelines with angiotensin converting enzyme inhibitorwith or without calcium channel blockers or betablockers. No change in their medication for
hypertension was registered during the fallow-up
period. After 2 months the average systolic bloodpressure 144,1 ± 6,60mmHg (5,5mmHg reduction,p<0.05) and average diastolic blood pressure was 88,3
± 2,67mmHg (3,8mmHg reduction, p<0,05). The
average HbA1c was 7,03 ± 0,27% which represents amuch better glucose control. Conclusion. SGLT-2
inhibitors in addition to improving glucose-control intype 2 diabetes patients they also have a beneficial
pleiotropic effect in reducing blood pressure. They act
by inhibiting the coupled reabsorption of sodium andglucose from the proximal tubules in the kidney. Thisway they increase renal glucose and sodium excretion.
It is well known that patients from Romania haveincreased sodium intake therefore this medication can
modulate the salt-responsive blood pressure
mechanisms.

P05. Changes in aged mice behavior
associated with fractalkine receptor
Ianis K. S. Boboc (1,2), Tudor A. Balseanu(2,3), Oana A. Docea (4), Maria Bogdan (1),Cornelia D. Calina (5), Bogdan Catalin (2,3)
1 University of Medicine and Pharmacy of Craiova, Faculty of
Pharmacy, Department of Pharmacology, Craiova, Romania;
2 Experimental Research Centre for Normal and Pathological
Aging, University of Medicine and Pharmacy of Craiova,
200349 Craiova, Romania; 3 University of Medicine andPharmacy Craiova, Faculty of Medicine, Department of
Functional Sciences, Craiova, Romania; 4 University of
Medicine and Pharmacy Craiova, Faculty of Pharmacy,
Department of Toxicology, Craiova, Romania; 5 University of
Medicine and Pharmacy Craiova, Faculty of Pharmacy,
Department of Clinical Pharmacy, Craiova, Romania.

Aim: Fractalkine is a multi-domain protein foundcommonly in the brain, particularly in neural cells. Its
receptor (CX3CR1) is known to be present on
microglial cells; interaction between this protein and its
unique receptor induces cell adhesion, chemotaxis,
crawling, “accessory cell” activity, and survival.
Fractalkine, via signaling through its receptor, may be
involved in modulating pathogenesis of several
inflammatory neurodegenerative diseases such as
multiple sclerosis, amyotrophic lateral sclerosis andAlzheimer disease. Fractalkine mediatedneuroprotection was attributed to recruitment of thenatural killer cell (subtype, NK1.1) a specific kind of
innate immune cell that expresses CX3CR1. Due tothose reasons we wanted to identify the behavioral
changes produced by fractakine in aged mice.
Methods: Aged transgenic TgH(CX3CR1-EGFP) mice
(80-96 weeks) were divided into 3 groups: CX3CR1+/+(n=8), CX3CR1+/- (n=12) and CX3CR1-/- (n=7) wereused. We performed several behavioral tests tohighlight the motor function (Open field, Cylinder test)
and cognitive impairments like social interaction (Social
chamber test), short-term memory (Novel object
recognition), compulsive, anxiety and depresion-likebehaviors (Marble burying, Nesting, Tail suspension, 0Maze, Hole board, Sucrose preference test). Results:
We identified several motor (moving velocity between
CX3CR1-/-, CX3CR1+/- compared to CX3CR1+/+) andcognitive (compulsive-like behavior CX3CR1-/-,CX3CR1+/- compared to CX3CR1+/+) behaivourchanges.Conclusion: Fractalkine and its specificreceptor appear to produce changes in the behavior ofaged animals in terms of both cognitive and motor
ability.

31

P06. EEG recordings of sleep/wake dynamics
changes in rats
Florin Zamfirache, Bogdan Amuzescu,
Beatrice Mihaela Radu
Department of Anatomy, Animal Physiology and Biophysics,
Faculty of Biology, University of Bucharest, Romania
Funding: Self-funded

P07. Effects of hypothermia as a therapeuticintervention in a model of neonatal cerebral
ischemia and hypoxia in rats
Toader, A. M., Harangus, I., Hoteiuc, O.,
Olanescu, C., Clichici, S., Mitrea, D.
Department of Physiology. Iuliu Hațieganu University of
Medicine and Pharmacy, Cluj Napoca, Romania

Introduction: The perinatal period is one of the mostvulnerable stages in the life of each individual, as theconsequences of hypoxic-ischemic damage may be
immediate, affecting the successful adaptation to
extrauterine life, and long-term, through the disruptionof normal brain development. Aims: The main objectiveof this study was to test the possible protective effectof hypothermia in hypoxic-ischemic encephalopathy at
newborn rats. Materials and methods: Theexperimental study was conducted at the Biobase
UMF “Iuliu Hațieganu” and the Biobase of the
Department of Physiology of the same University. The
material was represented by newborn Wistar rats,
males and females, with a weight of 10 g on average,
kept in optimal conditions along with their mothers.In
the 7th day post birth the hypoxic-ischemic injury is
performed, following Levine’s method, modified: underlocal anesthesia with lidocaine 2%, the common
carotid artery ligation was performed. The operation
was carried out under the microscope. After ischemia,
the animals were subjected to hypoxia, in bariatricchamber with a concentration of oxygen in the air of
8%, for 90 minutes. Subsequently each group ofanimals was divided into two subgroups, one being
cared for under normal temperature and the other inhypothermia with declining central temperature with
40C for 3 hours; then the animals were put to deathand the oxidative stress parameters were dosed frombrain homogenate. The study was completed byhistopathological and imunohistochemical examination,
for demonstration of Caspase 3 expression as amarker of apoptosis. Results: In neonatal hypoxicischemic encephalopathy hypothermia gives partial
neuroprotection by reducing the number of cells
expressing apoptosis in hippocampus, thalamus andcerebral cortex. Protein carbonyl level was decreased,
and antioxidant enzyme defence increased.
Conclusion: The results of this study prove that
hypothermia offers neuroprotection in hypoxic ischemic
brain injuries.

P08. Expression of sensory neuron-derived
CSF1 is spatially correlated with macrophageactivation after Spared nerve injury modelGrosu A. (1), Pertin M. (2), Kirschmann G. (2),Deftu A.F. (2), Ristoiu V. (1)(1) Department of Anatomy, Animal Physiology andBiophysics, Faculty of Biology, University of Bucharest,
Bucharest, Romania (2) Pain Center, Department ofAnesthesiology, Lausanne University Hospital and Universityof Lausanne (CHUV), Lausanne, Switzerland

Aims: Growing evidence suggests that macrophageactivation at the dorsal root ganglia (DRG) level andneuron-macrophage communication are essential
mechanisms underlying the pathogenesis of peripheral
neuropathic pain. The aim of this study was toinvestigate the expression of colony-stimulating factor 1(CSF1) and its potential role in macrophage
accumulation in the DRG after spared nerve injury(SNI) model of neuropathic pain. Methods: CX3CR1GFP transgenic mice were assigned to 3 groups:
Control (animals did not undergo any kind of surgery),Sham (the sciatic nerve was exposed) and SNI (thetibial and common peroneal rami of sciatic nerve wereligated and cut). Seven days after surgery, L3 and L4
DRGs were collected, frozen and cut and DRG
sections were double immunostained using antibodies
against NF200 or CGRP and against CSF1.Results:
CSF1 expression is significantly increased in sensory
neurons in both L3/L4 DRGs after SNI, but with ahigher expression in L4. This pattern is also observedin the macrophage accumulation, with the highest
degree of activation in L4, but still with a significant
number of activated cells in L3. Moreover, among
CSF1(+) neurons, 40% have peri-neuronal rings ofmacrophages in L4, while in L3 this percentage
decreases to 30%. Lastly, 50% of the CSF1(+) neurons
co-express NF200, a marker for large, myelinatedneurons, while less than 10% of them are small,
peptidergic neurons, co-expressing
CGRP.Conclusions: The pattern of CSF1 expression
after SNI is spatially correlated with macrophage
accumulation, suggesting its role in attracting
macrophages in DRGs after peripheral nerve injury.
Funding: This research was funded by UEFISCDI,
project no. PED 274/2020 and International Society for
Neurochemistry, through Educational grant (CAEN)
category 1A.

32

P09. Frey syndrome following parotid surgery
Nicoleta-Roxana Urzica (1,2); Diana Alina
Ciubotaru (1,2); Miruna Maria Gheorghisor (2);Constantin Caruntu (1,3); Ana Caruntu (2,4)(1) Department of Physiology, “Carol Davila” University of
Medicine and Pharmacy, Bucharest, Romania; (2)Department of Oral and Maxillofacial Surgery, “Carol Davila”
Central Military Emergency Hospital, Bucharest, Romania; (3)Department of Dermatology, “Prof. N.C. Paulescu” National
Institute of Diabetes, Nutrition and Metabolic Diseases,
Bucharest, Romania; (4) Department of Oral and Maxillofacial
Surgery, Faculty of Dental Medicine, “Titu Maiorescu”
University, Bucharest, Romania.

Background: Frey syndrome, also known as
auriculotemporal syndrome is characterized by
localized facial gustatory sweating and flushing and is
induced by aberrant reinnervation following injury to
the auriculotemporal nerve. Materials and Methods: In
our study, we present the implementation of the
Minor’s starch-iodine test, for confirming the diagnosis
in case of clinical suspicion of Frey syndrome following
parotid surgery.Results: Using this simple method, wewere able to objectify the clinical diagnosis of Frey
syndrome, based on patient’s reports of symptoms
such as facial warmth, flushing, and sweating in thesetting of acidic or spicy foods.Conclusion: Frey
syndrome can generate a considerable impact on thepatients’ quality of life. Thus, the clinicians must beaware of this clinical entity which may be frequently
encountered as consequence of parotidectomy, inorder to take the necessary preventive or therapeuticmeasures. We can use simple methods to confirm thediagnosis. However, further complex studies that aim
to clarify the mechanisms involved at the cellular andmolecular level could open new perspectives in nerve
regeneration research.

P10. Insights of aromataseimmunohistochemistry in invasive breast
cancer: importance of menopausal status
Ioana Armașu (1), Delia G. Ciobanu-Apostol(2), Victor Ianole (2), Ioana Vasiliu (1), Radu
Popescu (1), Roxana Barbu (1), Bogdan Stana(1), Dragomir N. Șerban (1), IonelaLăcrămioara Șerban (1)(1) Physiology Department, Faculty of Medicine, “Grigore T.
Popa” University of Medicine and Pharmacy Iasi, Romania; (2)Pathology Department, Faculty of Medicine, ”Grigore T. Popa”
University of Medicine and Pharmacy Iasi, Romania

Introduction: Aromatase is key enzyme in local
estrogen production by androgen conversion,
especially in women post-menopause. There havebeen controversies concerning aromatase localizationin human breast carcinomas. Also, aromataseinhibitors represent important drug class used to
manage hormone-sensitive breast cancer cases, butpatients that may benefit the treatment are currently
selected based on hormone (estrogen, progesterone)
receptors statuses, instead of intratumor aromataseimmunoreactivity.Patients and methods: Using
polyclonal antibody immunohistochemistry technique
we assessed (intensity and percentage scores) the
localization of aromatase in 70 breast cancer tissue
samples in order to assess immunostaining
characteristics relative to current histopathologicalvariables of breast carcinomas.Results: Aromatase
was found in all tissue compartments: tumor (95.7%),
stroma (58.6%) and adipose tissue (94.3%).
Aromatase expression in tumor cells inversely
correlated with tumor grading (ρ=-0.361, p=0.027), andcorrelated positively with ER (ρ=0.143, p<0.001).
Dividing the study group by age 55, tumor aromatase
expression was stronger correlated with ER (ρ=0.410,
p<0.001) in women aged <55y (pre- andperimenopause), but not in women aged >55y (postmenopause) (ρ=0.131, p=0.899). Although statisticalsignificance was not reached (p>0.05), negative
associations with fibrocystic breast disease (ρ=-0.342),
tumor grading (ρ=-0.385), PgR (ρ=-0.224), Ki67 (ρ=0.222), and a positive association with lymph nodeinvasion (ρ= 0.337) were observed in women aged
<55y, while in women >55y this association waspresent to a lesser extent only with tumor grading (ρ= 0.347) and Ki67 index (ρ= -0.133).Conclusion: Localaromatase was linked to better tumor differentiationand proliferation rate suggesting a potential prognostic
role in breast carcinomas.
Funding: This study was financed by internal grant fromthe “Grigore T. Popa” University of Medicine andPharmacy Iasi (no. 29024/28.12.2016).

33

P11. Kv3.3 subunits control presynaptic
waveform and improve timing at a central
excitatory synapse

P12. Morphological and histological changes
in the developing brain of Rfx4_v3 mutant
mice

Mihai Stancu (1), Amy Richardson (2), Victoria
Ciampani (2), Ian D. Forsythe (2) and Conny
Kopp-Scheinpflug (1)Mihaela Diaconu (1,2); Claudiu Gal (2,3); DianaCîrdei (1); Florentina Safciuc (4)(1) Division of Neurobiology, Department of Biology &Graduate School of Systemic Neurosciences, LudwigMaximilians University, Munich, Germany, (2) Auditory
Neurophysiology Laboratory, Department of Neuroscience,
Psychology & Behavior, College of Life Science, University ofLeicester, UK.

High-voltage activated potassium channels of the Kv3
gene family are key in rapidly repolarizing action
potentials (AP), supporting fast spikes and enablinghigh firing rate. Of the four Kv3 gene family members,
Kv3.1 and Kv3.3 are highly expressed throughout theauditory brainstem including the medial nucleus of the
trapezoid body (MNTB). It has been shown that MNTB
neurons possess functional Kv3 channels that arecomposed of either Kv3.1 and/or Kv3.3, and thedeletion of either subunit caused a small increase inpostsynaptic AP duration, consistent with functional
redundancy of either subunit in the postsynaptic MNTB
cell body. Here we test for Kv3 subunitspecific roles atthe presynaptic calyx of Held terminal innervating
MNTB neurons using in vivo single unit recordings in
Kv3.3 knockout mice. Extracellular recordings fromMNTB neurons exhibited a typical complex waveform,
comprised of a presynaptic and a postsynaptic
component. The time between the peak and trough ofextracellular APs are compelling markers for AP halfwidth and showed that the presynaptic Aps andsynaptic delays were significantly longer in Kv3.3
knockouts compared to WT recordings. These results
suggest that Kv3.3 is the presynaptic ‘delayed rectifier’,enabling fast presynaptic APs and precisely timed
synaptic delays. The changes in presynaptic AP
duration and synaptic delay in the Kv3.3 knockout arelikely to affect temporal processing in the MNTB
output, such as first spike latency and jitter. However,the longer presynaptic APs will also affect transmitter
release and hence spontaneous and sound driven
firing rates.
Funding: Biological Sciences Research Council
R001154/1, M016501, H2020 Health ITN LISTEN
722098, DFG SFB870 A-10

(1) Department of Biochemistry and Molecular Biology,
Faculty of Biology, University of Bucharest, Bucharest,
Romania; (2) Centre for Research and Technological
Development, Cantacuzino National Medical Military Institutefor Research and Development, Bucharest, Romania; (3)Faculty of Veterinary Medicine, University of Agricultural
Sciences and Veterinary Medicine, Bucharest, Romania; (4)Medical and Pharmaceutical Bionanotechnologies Laboratory,
Nicolae Simionescu Institute of Cellular Biology andPathology, Bucharest, Romania

Rfx4_v3 is the central nervous system proteoform ofRegulatory factor X4 (Rfx4). Interruption of a single
Rfx4_v3 allele prevented the formation of thesubcommissural organ, resulting in mice withcongenital hydrocephalus, whereas disruption of bothalleles caused failure of the dorsal midline brain
structure formation (Blackshear et al., 2003).
Additionally, Rfx4_v3 L298P homozygous mutant
mouse embryos (Zarbalis et al., 2004) resemble the
Rfx4_v3 null phenotype, being characterised bydorsoventral patterning defects in both telencephalon
and spinal cord (Asique et al., 2009). To further explore
the involvement of Rfx4_v3 into early brain patterning,
we analysed the mesencephalon andrhombencephalon of Rfx4_v3 L298P mouse embryos.
Genotyping was performed using variable 3’ end
method (Mitrecic et al., 2007) and sections of thedeveloping brain were stained by standard
hematoxylin-eosin and immunofluorescence
techniques. The mutant allele was inherited with a highfrequency (χ2 = 2.46, P < 0.05) and was hypomorphic,
resulting in heterozygous and mutant embryos withdifferent degrees of phenotypic severity. Collectively,
E12.5 mutant embryos presented doming of the skull orhydrocephalus in the telencephalon, which was greatly
enlarged at the expense of both mesencephalon andrhombencephalon. Furthermore, these embryos
showed a delay in the development of the 4th ventricle
choroid plexus and an ectopic expression of the
dopaminergic neurons in the ventral hindbrain. A
hypoplastic mesencephalon and an abnormal
proliferation of both isthmic and rhombomere 1 tissues
were noticed at E15.5. Mechanistically, Rfx4 functions
as a dimer and structural predictions suggested that
P298 mutation would disorganise its regulatory
dimerisation domain.
Funding: University of Bucharest, Faculty of Biology

34

P13. New insights into the ionizing radiation
effects at the cerebrovascular endothelium
level
Roberta Stoica (1,2), Mihai Radu (1), Liviu Craciun(3), Ioan Cenusa (4), Beatrice Mihaela Radu (2)(1) Department of Life and Environmetal Physics, Horia
Hulubei National Institute for Physics and Nuclear
Engineering, (2) Department of Anatomy, Animal Physiology
and Biophysics, Faculty of Biology, University of Bucharest,
Bucharest, Romania, (3) Department of Applied Nuclear
Physics, Horia Hulubei National Institute for Physics andNuclear Engineering, (4) Department of Radioisotopes andRadiation Metrology, Horia Hulubei National Institute forPhysics and Nuclear Engineering

According to WHO, brain tumors represent nowadays
the 10th cause of death and researchers consider that
one of the most effective treatments is radiotherapy.
Brain radiotherapy was proved to induce long term
irreversible cognitive impairment. Considering the roleof BBB in regulation and protection of the brain
microenvironment, a complex characterization of theeffects induced by irradiation at therapeutic doses on
the brain microvasculature is imposed. We observed
the cytotoxic, functional and genotoxic effects after
low-energy accelerated proton irradiation upon an invitro model of murine cerebral microvasculature(bEnd.3 cell line, ATCC). Using the beam line of TR19
cyclotron, we exposed cells to doses in the range 0-10
Gy, (dose rate: 1 Gy/ min). The cells proliferation andsurviving rates in stress-induced conditions, the DNA
damage, the reactive oxygen species formation, thecalcium ions dynamics and the cellular capacity of
migration at various time intervals post-irradiation wereassayed. For comparison X-ray irradiation was used.
As results, we observed an inhibition (~90%) of thecellular proliferation and a strong increase of
micronuclei number at doses over 5 Gy, a reduction of
the DNA repair capacity by the increased values of thedose (~100%) and the linear energy transfer- LET(~20%) and also a decrease of the cell relative
migration rate (~25%). In conclusion, we observed asignificant modification of the measured parameterswith the dose increase and the LET values. Our study
presents preliminary results regarding the BBB
endothelial cells behavior in oxidative stress conditions
induced by the 2 most used radiotherapy methods,
protons and X-ray radiation.

P14. Plasma Biomarkers of Stroke
Mihai Andrei Ruscu (1), Andreea Mihaela Cercel (1),Roxana Surugiu (1), Daiana Burdusel (1), Olga
Neustroeva (2), Tarja Malm (2), Aurel Popa-Wagner(1*)(1) University of Medicine and Pharmacy of Craiova,
Biochemistry, Neurobiology of Aging Group, Romania. (2)Tarja Malm - University of Eastern Finland A.I. Virtanen
Institute for Molecular Sciences. (1*) Corresponding author

Ischemic stroke is an acute disease which often results
in severe long-term physical disability, depression, andcognitive decline. To date, patients at risk for these lateconsequences of stroke are not duly diagnosed andtreated due to the lack of reliable biomarkers.
Extracellular vesicles derived from neurons (ND-EVs)
enter the blood stream and have been shown to reflect
neuronal health. Previous work by iBioStroke partners
found that miR21 and miR223 are hypoxia inducible
and secreted into EVs both in stroke models and stroke
patients that were significantly associated with clinicaloutcome (measured by modified Rankin Scale, mRS)
in poststroke patients at 90 days. In addition, two
Genome Wide Association studies have found genetic
polymorphisms associated with stroke recovery. Our
hypothesis is that neuronal-derived EVs (ND-EVs)
released into blood and/or CSF can be used as
biomarkers for stroke outcome. Our aims are (1)isolating ND-EVs released into blood and CSF in aged
mice and rats and patients following ischemic stroke,(2) using proteomics and transcriptomics to identify
novel ND-EV-based biomarkers for the prediction of
stroke outcome, (3) validate ND-EV-based biomarkers
in two highly stratified stroke patient populations, and(4) cross-validate ND-EV-based biomarkers found inaged animal models in a cohort of stroke patients.
Thereby novel ND-EV based biomarkers might be able
to predict long-term outcome after ischemic.

35

P15. Post-stroke transcriptomics: lessons
from the juvenile brain
Abuzan Mihaela, Ruscu Mihai Andrei, Surgiu
Roxana, Aurel Popa-Wagner
University of Medicine and Pharmacy of Craiova,
Biochemistry, Neurobiology of Aging Group, Romania

Post-stroke transcriptomics: Lessons from the juvenile
brain. A significant number of genes are regulated inorder to promote brain repair after a lesion. The kinesin
superfamily proteins (KIFs), including KIF1b, KIF4,
KIF21b and KIF26b are essential for morphogenesis
and functioning of the cell. However, their role inaxonal regeneration after injury is still not wellunderstood. Here, we asked if injured young adultbrain tissue can re-express developmental genes thatwere active during early postnatal brain development.
By RT-PCR and immunohistochemistry, the brains of 3days old juvenile rat pups showed high levels of kif1b,
kif4, kif21b and kif26b transcripts as well as high levelsof KIF4 protein. However, of these only kif1b and kif4
mRNAs and KIF4 were highly re-expressed in thesubventricular zone and perilesional cortex of young
adult rats. The regenerative capacity was limited to the
NPCs in the subventricular zone and endothelial cellsof the inflamed blood vessels. Most interesting, KIF4
was also sporadically re-expressed in some surviving
neurons in the peri-lesional area, that have been, most
likely, contributed by NPCs in the leptomeninges.
Conclusion: These results suggest that the young-adultbrain has a limited capacity to re-express juvenile
genes needed for axonal growth. Indeed, the injured
young adult brain recapitulates in part, kinesins geneand protein expression pattern seen during early
postnatal brain development.

P16. Reflectance confocal microscopy for invivo evaluation of Meissner’s corpuscles indiabetes mellitus
Andreea-Mariana Matei (1), Constantin Caruntu(1,2), Daniel Boda (2,3), Mihaela Adriana Ilie (4)(1) Department of Physiology, “Carol Davila” University of
Medicine and Pharmacy, Bucharest, Romania; (2)Department of Dermatology, “Prof. N. Paulescu” National
Institute of Diabetes Nutrition and Metabolic Diseases,
Bucharest, Romania; (3) Dermatology Research Laboratory,“Carol Davila” University of Medicine and Pharmacy,
Bucharest, Romania; (4) Dermatology Department, Kalmar
County Hospital, Kalmar, Sweden.

Diabetes is a major health care problem and its
associated complications, are causes of significant
morbidity and mortality. Neuropathy is the mostcommon complication of diabetes and its diagnosis,
especially in early stages, is a significant challenge forboth research and clinical practice. Meissnercorpuscles are complex sensory receptors of theglabrous skin, involved in light touch sensitivity. The
density of Meissner corpuscles is a sensitive marker indifferent types of sensory neuropathies and iscorrelated with the density of intraepidermal nerve
fibers. Reflectance confocal microscopy is a modern
imaging technique which allows the
micromorphological and functional investigation of skinstructures in vivo and in real time, with a similar
resolution with histological examination. Here we
investigate the changes in density of Meissnercorpuscles associated with diabetes mellitus, andevaluate their morphological alterations corelated withdiabetic neuropathy. The recent advances in skinimaging and in vivo investigation of cutaneous nerve
structures are very promising and could improve theearly diagnosis of nerve impairment ensuring timely
treatment of the disease. This work was supported by agrant of the Ministry of Research, Innovation and
Digitization, CCCDI - UEFISCDI, project number PN-IIIP2-2.1-PED-2021-2243, within PNCDI III
Funding: This work was supported by a grant of the
Ministry of Research, Innovation and Digitization,
CCCDI - UEFISCDI, project number PN-III-P2-2.1PED-2021-2243, within PNCDI III

36

P17. The effect of extreme sleep durations on
cardiovascular healthDidina Cătălina Barbălată (1); Mara Ioana Ieșanu
(1,2); Ioana Ștefănescu (1); Adelina Vlad (1)(1) Physiology Department, Faculty of Medicine, Carol
Davila University of Medicine and Pharmacy, Bucharest,
Romania; (2) Marie Curie Children’s Clinical Hospital,
Bucharest, Romania

Introduction: Excessive or reduced sleep durations ((≤6h/24h or ≥9h/24h) have been associated with anincreased incidence of cardiovascular disease (CVD).
Several studies propose a diverse array of underlying
mechanisms, but only few of them provide a thoroughassessment. Materials & Methods: 23 studies wereselected following a systematic literature search(PubMed, published in the last 7 years). Articles
describing CVD impact on sleep were excluded.
Results: Extreme sleep durations have a 35% higher
mortality risk of coronary heart disease. Both shortand long habitual sleep associate metabolic
dysregulation, leading to chronic inflammation andincreased pro-atherogenic environment.
Observational studies have shown that shortsleepers, compared to peers sleeping 7- 8 h, are≈60% more likely to develop hypertension, have a≈20% higher risk of myocardial infarction and a ≈30%
higher incidence of left ventricular hypertrophy.
People with insomnia, a health problem affecting 1030% of the general population are 45% more likely todevelop or die from CVD. The responsible
mechanism seems to be increased atherogenesis due
to high production of angiotensin II. Atherosclerotic
lesions and increased levels of Ly-6C monocytes
have been observed in sleep deprived mice as well.
Habitual prolonged sleep duration has been
associated with CVD risk, although studies examining
the underlying mechanisms are rare. Long sleepers
often had insulin dysregulation. However, prolonged
sleep was linked to decreased HDL levels, an antiatherogenic biomarker. Besides the biologicalabnormalities, the lifestyle of long sleepers should betaken into consideration as long sleepers are more
prone to engage in CVD-promoting behaviours(insufficient exercise, smoking, increased alcohol
intake). It has been shown that the long sleepers’ riskof diabetes may ameliorate by adopting a healthierlifestyle (improved diet, increased exercise).
Conclusion: Although observational data andbiological evidence suggest a relationship between
extreme sleep durations and CVD, additional
experimental investigation is required to elucidate themechanistic pathways behind it. Based on theavailable data, we hypothesise that irregular sleep
patterns provoke CVD via metabolic alterations. It
should be taken into consideration that the proatherogenic environment thus created may beworsened by unhealthy behaviours. As both short andlong sleep durations may be risk factors for the
emergence of chronic diseases, we recommend
assessing sleep length during clinical evaluations.

P18. The impact of Vitis Vinifera L. extract on
behavioral changes and redox imbalance inhippocampus and frontal lobe of Wistar rats
with experimental menopause
Maria Cristina Olănescu Vaida Voevod, Irina
Nechita, Alexandra Cristina Sevastre-Berghian,
Cristina Bidian, Oana Alina Hoteiuc, Gabriela
Adriana Filip
Physiology Department, Faculty of Medicine, University Iuliu
Hatieganu, Cluj-Napoca, Romania

Background. The decline in estrogen levels inmenopause is accompanied by higher risk for
cardiovascular and neurodegenerative diseases andchanges in physiological processes, including cognitiveand motor functions. Menopause-induced alterations in
structure and function of hippocampal and corticalcircuits could be attenuated by administration of grape
extract due to neuroprotective, antioxidant andscavenger properties of grape polyphenols. Aims. Our
study aimed to assess the impact of Vitis Vinifera L.
(VV) extract on behavioral changes (generallocomotion and anxiety like behavior) and oxidative
stress in brain in an experimental model of menopause
induced by ovariectomy (OV) in Wistar rats. Methods.
For each subset of experiments (I and II), 20 male
Wistar rats were divided into 4 groups (n=5): animals
with sham ovariectomy (SOV) treated with vehicle(SOV+veh), SOV treated with VV extract (SOV+VV),
OV treated with vehicle (OV+veh), and OV treated with
VV (OV+VV). Vitis Vinifera L. extract (30 mg/kg b.w
solved in 0.5 ml water) or vehicle (0.5 ml water) wereorally administered for 21 days (subset I) and 42 days
(subset II), after the surgery, according to the groupprotocol. The behavioral tests (open field test – OFT
and elevated plus maze - EPM) were conducted after
21 and 42 days, and the malondialdehyde (MDA) andnitrotyrosine (NTZ) levels from frontal lobe andhippocampus were evaluated 24h after the last
behavioral test. Results. OV has been shown toincrease the level of oxidative stress and have anegative impact on memory, behavior and motor
functions of rats. OV reduced, after 21 days, thegeneral locomotion in OFT (p<0.001) and motor activity
in EPM (p<0.001) without significant changes inanxiety-like behavior. After 42 days, the generallocomotion and motor activity were kept at low level(p<0.05) but the anxiety behavior (p<0.01; p<0.001)
improved significantly. 21 days of VV administration
triggered mostly non-significant increases of generallocomotion indicators in OFT and EPM and nonsignificant decreases of the anxiety level in EPM. After
42 days, VV extract improved both general locomotionin OFT and motor activity in EPM (p<0.05) anddiminished significantly the anxiety (p<0.05, p<0.01).
The MDA levels (p<0.05, p<0.001) and tyrosineoxidation (p<0.01; p<0.05) decreased after VV
treatment in the frontal lobe, both at 21 days and 42days, while in hippocampus VV extract had
controversial effects, with minimal decreases of MDA
and high levels of NTZ (p<0.05), especially after 42days of treatment. Conclusions. Our findings suggest

37that Vitis Vinifera L administration for a long period,
may have beneficial effects on both locomotion andemotionality and could also have antioxidant properties
in menopause, especially in frontal lobe.

P19. The role of music study for aharmonious development of the brain
Daniel-Alex MilencoviciȘcoala Doctorală de Muzică și Teatru, Universitatea de Vest
din Timișoara

Recent research has found that people who study amusical instrument benefit from excellent brain
training. Scientists have concluded that simply playing
an instrument can actually alter the shape of the brain
and its native abilities, including from the perspectiveof increasing the intelligence quotient, both in children
and adults. Studying a musical instrument is, for thebrain, the equivalent of an intense fitness training,which works the entire muscles of the body at thesame time. Specialists have gathered evidence thatthe brain regions of musicians are different from thoseof people who do not practice this art, structurally andfunctionally. These are the areas of the brain
responsible for motor skills, hearing, memory, andhearing information that become more active when aperson plays an instrument. This artistic preoccupation
can improve important skills in everyday life, such as
alertness, action planning or perception of emotions.
The entire architecture of the brain changes amid
music created with the help of a musical instrument,
resulting in a whole series of benefits confirmed byexperts. In this study, I would like to present just a few
of these benefits: improved memory, training
perseverance, improved body coordination, increased
ability to focus and stress relief. I will also present
some experienced exercises in the class of students.