bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional and epigenetic control of cranial bone lineage development
Authors: Atit Radhika P 
Published: June 2021

During development, proper spatiotemporal patterning and specification of tissues requires precisely orchestrated changes in gene expression, which are regulated by transcription factors and epigenetic modification in response to instructive cues from cell signaling pathways. Development of the skull bones requires the coordination of two stem progenitor populations, the cranial neural crest cells (CNCC) and head paraxial mesoderm (PM), to ensure cell fate selection and morphogenesis. We previously demonstrated that Wnt/β‐catenin signaling acts as a molecular switch in the cranial mesenchyme by simultaneously specifying cranial bone and dermal lineages and repressing cartilage cell fate. We identified Wnt signaling and TWIST1 function in a feed‐forward loop to sustain Wnt signaling and promote the differentiation of calvarial bone progenitors. In order to understand the function of epigenetic mechanisms calvarial bone development at different developmental stages, we conditionally deleted Ezh2 which is part of the Polycomb Repressive Complex 2 in a stage‐specific manner in vivo. We found that Ezh2 is required early and transiently to promote bone progenitor commitment. Inhibition of retinoic acid (RA) signaling in Ezh2 mutants in vivo rescues calvarial bone development, and RA signaling activation in the conditional Ezh2 background leads to synergistic activation of anti‐osteogenic factors, such as Hand2 and HoxC8. Our results suggest that RA signaling and Ezh2 can function in parallel in an incoherent type1 feed forward loop to balance the suppression of anti‐osteogenic factors to permit later differentiation events in the calvarial bone lineage program. Our data provide new insights into the dynamic gene regulation during the specification of calvarial bones and commitment to intramembranous bone formation.Support or Funding InformationNIH‐NIDCR DE‐01870This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Decreased Number of Brainstem Serotonin (5‐HT) Neurons During Chronic Hypercapnia in Goats
Authors: Buchholz Kirstyn , Burgraff Nicholas , LeClaire John , Neumueller Suzanne , Pan Lawrence , Hodges Matthew , Forster Hubert 
Published: June 2021

Thirty days after carotid body denervation (CBD) in goats, the number of neurons expressing the rate limiting enzyme for serotonin (5‐HT) synthesis (tryptophan hydroxylase, TPH), in the medullary raphe nuclei (MRN) and the ventrolateral medulla (VLM), was 50% of that in control goats (J. Appl. Physiol. 115, 1088–1098, 2013). This difference could be due to loss of carotid afferents per se, or it could be secondary to the CBD induced chronic hypercapnia. The objective of the present study was to assess the effect of hypercapnia per se on TPH expressing neurons in the MRN and VLM. To achieve the objective, we constructed environmental chambers to chronically house and study the effects of chronic hypercapnia in adult goats. Following a room air control period, the goats were exposed to either room air or an elevated inspired CO2 (InCO2) of 6% for 30‐days. After 30 days of hypercapnia, the brainstems were harvested and immunohistochemistry and western blots were used to determine whether chronic hypercapnia altered the number of TPH expressing neurons in the MRN and VLM. We found that there was a nearly 50% decrease (P<0.01) in the number of neurons expressing TPH within both the MRN and VLM. Additionally, there was a decline in the number of total neurons within these nuclei, suggesting that the loss of TPH expressing neurons may be from neuronal death. We conclude that chronic hypercapnia per se has a major impact on the 5‐HT neuromodulatory system which is important in the control of breathing.Support or Funding Information

The Department of Veteran Affairs
NIH Grant 007852
This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
S‐Nitrosoglutathione Reductase Inhibition Attenuates Airway Hyperreactivity in a Neonatal Hyperoxia‐Exposed Mouse Model
Authors: Sopi Ramadan B , MacFarlane Peter M , Gaston Benjamin , Martin Richard J , Raffay Thomas M 
Published: June 2021

Premature infants exposed to supplemental oxygen are at risk for developing wheezing disorders and airway hyperreactivity (AHR). We have previously shown that the endogenous smooth muscle relaxant molecule, S‐nitrosoglutathione (GSNO), is degraded in neonatal hyperoxia by upregulated GSNO reductase (GSNOR) in the murine lung (Raffay, et al. Molecular Pharmacology 2016; 90(4):418–26). We hypothesize that inhibition or deletion of GSNOR will attenuate hyperoxia‐induced AHR in this neonatal mouse model. Newborn C57BL/6 wild‐type (background) or GSNOR−/− (knockout) mice were randomized on the first day of life and assigned to room air (21% O2) or hyperoxic (60% O2) groups for three weeks. At day P21, AHR was assessed in vitro using precision‐cut living lung slice preparations in response to increasing doses of bath‐applied methacholine (MCh, 0.25–64 μM). Wild‐type lung slices were pre‐incubated overnight with or without a GSNOR inhibitor (100 μM N6022). AHR is reported as percent change in airway lumen area from baseline (±SEM). 2–3 airways were imaged and averaged per animal per condition. Neonatal hyperoxia significantly increased (p<0.001) airway contractile responses to MCh in wild‐type mice with a mean maximal effect (Emax) of 70.4 ± 2.1% compared to the room air control Emax of 44.5 ± 9.1%. GSNOR inhibition significantly reduced airway contractile responses in wild‐type hyperoxic slices to 34.1 ± 4.2% (p<0.001). GSNOR−/− mice exposed to hyperoxia did not display increased airway contractile responses (Emax= 50.9 ± 5.5%). These studies show that neonatal hyperoxia‐exposed mice display in vitro AHR to methacholine and that inhibition or deletion of GSNOR attenuates hyperoxia‐induced AHR. We speculate that increased lung GSNOR expression is critical for neonatal hyperoxic bronchoconstriction. GSNO‐based therapies may serve as novel treatments for premature patients with AHR.Support or Funding InformationSupported by NIH 5K08HL133459‐02 and ATS Foundation Unrestricted Research GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of voluntary movement with non‐dominant finger on the delay time of involuntary movement in a patient of mirror movement disorder
Authors: Ito Kimiko , Abe Chikara , Taketani Takeshi 
Published: June 2021

Mirror movement disorder is a condition in which intentional movements of one side of the body are mirrored by involuntary movements of the other side. This symptom is mainly observed in the distal upper limbs. Mirror movement disorder is present in patients with a variety of movement disorders, such as dystonia, Parkinson's disease, and essential tremor as well as in congenital nervous system disorders. Mirror movement disorder is also observed in healthy subjects even in several members of the same family with no other neurological signs (Congenital mirror movement disorder). Although it is known that mutations in the DCC or RAD51 gene is involved in the congenital mirror movement disorder, it is still far from the understanding of the mechanism in congenital mirror movement disorder since its prevalence is thought to be less than 1 in 1 million. In this study, we found the healthy child and her father who had mirror movement. We report the quantitative analysis of the mirror movement using videotape recording. We obtained informed consent for the videotape recording and the experimental procedures from all subjects. In the subject of the child, we recorded the movement of both index fingers during pressing the button of the picture book by right index finger. The movement of the left index finger was observed 33 ms after pressing, and the maximum speed of the movement was comparable. In the subject of her father, we recorded the movement of both fingers during we asked him to move right or left one finger. The delay time between right (dominant) and left (non‐dominant) fingers was 24 ± 8 ms when we asked him to move the dominant finger. However, this value was significantly increased when the non‐dominant fingers were asked to move (133 ± 47 ms). In conclusion, child and her father had same symptoms; the involuntary movement was observed after voluntary movement with delay time. Increased delay time between voluntary and involuntary movement during the non‐dominant fingers were asked to move might be due to use‐dependent plasticity. This should be studied in the future study with anatomical/physiological examination of the brain and comprehensive inspection of genes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of smartphone light on the physiology signal and cognitive function in circadian environment
Authors: Lee Minkyung , Hong Yonggeun 
Published: June 2021

Many people are constantly exposed to artificial light caused by digital devices such as computer, smartphone, and TV. Prolonged exposure to artificial light disturbs our circadian rhythm, cognitive function and autonomic nervous system (ANS). Therefore, this study aimed to analyze the alterations in physiological signals and cognitive functions following exposure to smartphone light in order to confirm the effects of artificial light on the human body. Normal adults aged from 21 to 28 were engaged in this study. The experiments were conducted in day (10:00~14:00) and night (8:00~12:00) conditions. Experimental subjects were divided into three groups according to smartphone screen brightness; 50%, 100%, and blue light filter (BLF), then used smartphone for 10 min/set (rest time: 5 min) and repeated the task three times. The ANS changes were confirmed using pulse pressure measurement equipment. Short‐term memory (STM), long‐term memory (LTM), and recognition tests were conducted via language memory test (LMT) and visual memory test (VMT). After using smartphone at daytime condition, 50% group shoed significantly increased ANS activity. Also, LTM and recognition were significantly increased in the 50% and BLP group. In night condition, however, BLF group showed increased LTM and recognition. It has been demonstrated by this study that smartphone light may influence ANS, memory, and cognitive functions. Accordingly, blue light filter is recommended when using smartphone to reduce such harmful alterations.Support or Funding InformationFunds: NRF‐2017R1A2A2A01067169, KGM4611821, 2016 Creative Research Program of Inje University, Republic of KoreaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The &[Alpha]2δ‐1–NMDA Receptor Coupling is Essential for Corticostriatal Long‐Term Potentiation and is Involved in Learning and Memory
Authors: ZHOU JINGJING , Li De‐Pei , Chen Shao‐Rui , Luo Yi , Pan Hui‐Lin 
Published: June 2021

The striatum receives extensive cortical input and plays a prominent role in motor learning and habit formation. Glutamate N‐methyl‐Daspartate (NMDA) receptor (NMDAR)‐mediated long‐term potentiation (LTP) is a major synaptic plasticity involved in learning and memory. However, the molecular mechanism underlying NMDAR plasticity in corticostriatal LTP is unclear. Here, we show that theta‐burst stimulation (TBS) consistently induced corticostriatal LTP and increased the coincident presynaptic and postsynaptic NMDAR activity of medium spiny neurons. We also found that α2δ‐1 (previously known as a subunit of voltage‐gated calcium channels; encoded by the Cacna2d1 gene) physically interacted with NMDARs in the striatum of mice and humans, indicating that this crosstalk is conserved across species. Strikingly, inhibiting α2δ‐1 trafficking with gabapentin or disrupting the α2δ‐1–NMDAR interaction with an α2δ‐1 C‐terminus–interfering peptide abolished TBS‐induced LTP. In Cacna2d1‐knockout mice, TBS failed to induce corticostriatal LTP and the associated increases in presynaptic and postsynaptic NMDAR activities. Moreover, systemic gabapentin treatment, microinjection of α2δ‐1 C‐terminus–interfering peptide into the dorsomedial striatum, or Cacna2d1 ablation impaired the alternation T‐maze task and rotarod performance in mice. Our findings indicate that the interaction between α2δ‐1 and NMDARs is of high physiological relevance and that a TBS‐induced switch from α2δ‐1–free to α2δ‐1–bound NMDARs is critically involved in corticostriatal LTP and LTP‐associated learning and memory. Gabapentinoids may adversely affect cognitive function by targeting α2δ‐1–NMDAR complexes.Support or Funding InformationHuman brain tissues were obtained from the Harvard Brain Tissue Resources Center, a NeuroBioBank Repository funded by the National Institutes of Health. This work was supported by the National Institutes of Health (GM120844 and NS101880 to H.‐L.P.) and by the N.G. and Helen T. Hawkins Endowment.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise‐augmentation of fear extinction depends on mTOR signaling
Authors: Smith Abigail Marilyn , Moya Nicolette , Tanner Margaret , Balolia Aleezah , Davis Jazmyne , Loetz Esteban , Jaime Jennifer , Greenwood Benjamin 
Published: June 2021

Exercise has beneficial effects on cognition and mental health, such as enhancing the extinction of a traumatic memory. Rats allowed to run in a wheel for a single, two‐hour session immediately following fear extinction training show enhanced fear extinction memory. The mechanisms by which exercise augments fear extinction are unknown. The mammalian target of rapamycin (mTOR) is a translation regulator involved in synaptic plasticity, and is a target of cellular signals sensitive to exercise. Chronic exercise increases mTOR signaling in brain regions involved in extinction learning, but whether a single bout of exercise capable of enhancing fear extinction increases mTOR is also unknown. The goal of this study was to determine if a single session of wheel running increases mTOR signaling and, if so, whether mTOR signaling contributes to the exercise‐augmentation of fear extinction. Adult, male Long Evans rats exposed to auditory fear conditioning received intracerebral‐ventricular injections of the mTOR inhibitor rapamycin prior to fear extinction training. Immediately after fear extinction training, rats were placed in locked or mobile running wheel for two hours. Post‐extinction exercise enhanced fear extinction memory retrieval the following day, and this effect was blocked by rapamycin.Moreover, an acute bout of exercise increased mTOR signaling in several regions involved in memory and fear extinction. The increase in mTOR signaling produced by exercise was also blocked by rapamycin. These data suggest that acute exercise enhances fear extinction through a mechanism involving mTOR signaling.Support or Funding InformationSupported by the Undergraduate Research Opportunity Program, 2 T34 GM096958‐06, and NIH MH114992This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of the Dorsal Striatum in Fear Extinction and Relapse
Authors: Balolia Aleezah , Tanner Margaret K , Moya Nicolette A , Wiseman John R , Loetz Esteban C , Davis Jazmyne KP , Jaime Jennifer , Oleson Erik B , Greenwood Benjamin 
Published: June 2021

The poor long‐term success of fear extinction‐based exposure therapy for post‐traumatic stress disorder (PTSD) is often caused by the relapse of previously extinguished fear. We have previously observed that activation of substantia nigra (SN) dopamine (DA) neurons during fear extinction enhances extinction memory and reduces renewal. Although the specific targets mediating the effects of SN DA on extinction are unknown, their identification could pave the way for the development of novel strategies to reduce fear relapse in PTSD patients. A primary target of SN DA is the dorsal striatum, which consists of two regions: The dorsomedial striatum (DMS), responsible for goal directed learning, and the dorsolateral striatum (DLS), concerning more inflexible, habitual behaviors. The goal of these experiments was to begin to investigate the roles of the DMS and DLS in fear extinction and relapse in adult, male Long Evans rats. Inactivation of the DLS during auditory fear extinction with a Muscimol/Baclofen cocktail (0.03/0.3 nmol/uL) enhanced fear extinction memory but had no effect on fear renewal, while inactivation of the DMS prevented renewal, but had no effect on extinction memory in the extinction context. To investigate the involvement of DA, D1 receptor signaling was blocked in either the DMS or DLS during fear extinction. D1 blockade in the DMS impaired extinction retrieval in the extinction context, but the extinction memory remained susceptible to renewal. D1 blockade in the DLS had no effect on extinction memory or renewal. Despite this, optogenetic stimulation of SN terminals in the DLS during fear extinction reduced fear renewal without impacting extinction memory in the extinction context. These results suggest that the DMS and DLS play different roles in fear extinction and relapse. The DMS supports context‐specific fear extinction through a mechanism involving D1 receptor signaling. Although the contribution of the DLS to normal fear extinction is minimal, fear extinction memory can be rendered resistant to renewal by manipulations that increase the role of the DLS in extinction (DMS inactivation, optogenetic stimulation). Manipulations that increase the involvement of the DLS in fear extinction, such as exercise, could therefore represent effective augmentation strategies for fear extinction in order to reduce relapse.Support or Funding InformationNIH grant 068283 NIH grant 2 T34 GM096958‐06This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiovascular and autonomic modulation in trained rats: effects of iNOS inhibition and oxidative balance in the rostroventrolateral medulla
Authors: Martins‐Pinge Marli Cardoso , de Ataides Raquel Hiviny , Michelini Lisete 
Published: June 2021

We proposed to investigate the participation of the inducible nitric oxide synthase (iNOS) on glutamatergic neurotransmission and the oxidative profile in the rostral ventrolateral medulla (RVLM) in trained rats. Wistar rats were submitted to physical training (T) protocol or sedentary (S) for 4 weeks. After the last swimming session, the animals were submitted to guide cannulae implantation directed to RVLM. After 3 days of surgical recovery, femoral artery and vein catheterization were performed for direct recording of mean arterial pressure (MAP) and heart rate (HR). The acquired cardiovascular data underwent spectral analysis (Cardio Series®).An inhibitor of iNOS (aminoguanidine, 250pmol/100nl) was unilaterally microinjected into the RVLM. Other animals received microinjection of glutamate (5nmol/100nl) in RVLM, before and after of the aminoguanidine. Bilateral punchs of RVLM were collected for analysis of iNOS gene expression (real‐time PCR); quantification of reduced glutathione and lipid peroxidation (spectrophotometer); iron‐reducing antioxidant (FRAP) and ABTS radical scavenger (Multiskan GO ThermoScientific®). T Animals presented a reduction in the gene expression of iNOS in RVLM associated to rest bradycardia (S: 371±8 vs. T: 312±8 b/min, r2= 0.58) and higher antioxidant capacity (FRAP; S: 5±1 vs. T: 9±1.3 nmol Trolox Eq/mg protein). Swimming improved baroreflex sensitivity (S: 1.04±0.06 vs. T: 2.4±0.28 ms2/mmHg2) and lower sympathovagal ratio (LF/HF, S: 0.6±0.09 vs. T: 0.2±0.02). In T rats, the inhibition of iNOS in RVLM caused a lower pressor response (ΔMAP: S: 32±3 vs. T: 20±2 mm/Hg) and tachycardia (ΔHR: S: 55±4 vs. T: 43±1 b/min), abolishing previous differences in HR variability between groups. The microinjection of glutamate in RVLM of T group caused a lower pressor response (ΔMAP: S: 60±6 vs. T: 41±2 mmHg) and tachycardia (ΔHR: S: 90±4 vs. T: 58±3 b/min) and after iNOS inhibition in RVLM, we observed a greater glutamatergic response in T animals (ΔMAP: 69±3 mmHg). In conclusion, the cardiovascular benefits of physical training can be associated with decreased modulation by NO in RVLM via iNOS and also reduction of oxidative stress in this vasomotor center.Support or Funding InformationCAPES (felowship)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ionotropic and Metabotropic Glutamate Receptors Contribute to Cardiorespiratory Responses to Inhibition of Astrocytic Excitatory Amino Acid Transporters
Authors: Martinez Diana , Friskey Sarah , Kline David , Hasser Eileen 
Published: June 2021

The nucleus tractus solitarii (nTS) is the initial site of termination of cardiorespiratory afferents, which transmit signals through release of glutamate (Glu). Afferent information is integrated extensively in the nTS, thus shaping its output and cardiorespiratory responses. We have shown that inhibition of astrocytic excitatory amino acid transporter 2 (EAAT2) in the nTS increased ambient [Glu] and altered basal and reflex cardiorespiratory function. These effects were partially blocked by ionotropic glutamate receptor (iGluR) antagonism. We hypothesized that the responses remaining after iGluR blockade were due to activation of metabotropic (m)GluRs. To test this, Inactin‐anesthetized rats were instrumented to record mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic and phrenic nerve activity (SSNA; PhNA), and for microinjections into the nTS. The general EAAT inhibitor TFB‐TBOA (10 μM, 90 nl) was microinjected unilaterally into the nTS. GluR antagonists or vehicle (aCSF) were then microinjected, followed by two additional injections of TBOA. Unilateral nTS microinjection of TBOA decreased MAP, HR, PhNA and SSNA, consistent with effects of increased [Glu] in the nTS. Following aCSF, additional injections of TBOA produced augmented as well as prolonged cardiorespiratory responses. Prior blockade of iGluRs with a cocktail (90 nl) of NBQX (2 mM) and AP5 (10 mM) reduced the response to EAAT inhibition. However, it did not prevent the augmented effects of repetitive TBOA, indicating a role for other receptors. The effects of combined blockade of iGluRs and Group II/III mGluRs (MSOP, 100 mM + eGlu, 10 mM; 90 nl total) were similar to those of iGluR antagonism alone. In contrast, combined blockade of iGluRs and Group I mGluRs (LY367385, 10 mM; 90 nl total) blunted the cardiorespiratory effects of nTS EAAT inhibition, and markedly attenuated enhanced responses to subsequent injection of TBOA. These data are consistent with the concept that nTS inhibition of astrocytic EAATs increases [Glu], producing cardiorespiratory responses similar to excitation of nTS neurons involved in baroreflex function. These effects of EAAT inhibition are mediated primarily by iGluRs and Group I mGluRs. It is possible that Group II/III mGluRs also contribute via other mechanisms.Support or Funding InformationSupported by HL132836 and HL128454This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.