bluuebunny/crossref_metadata_2025 huggingface dataset:
The autistic mind in the light of neuropsychological studies
Authors: E. Pisula
Published: November 2023

The underlying causes of autism spectrum disorders have not yet been identified. There is a group of theories which attempt to explain the source of difficulties experienced by people with these disorders through neurocognitive deficits. The most popular among them refer to deficits in theory of mind, executive dysfunction and weak central coherence. The results of over 20 years of research show that although these deficits may at least partially explain variations in the course of social development, communication difficulties and the formation of rigid patterns of behavior and interests in individuals with autism, none of them is sufficient on its own to comprehensively explain the complex picture of autistic disorders. Information about the neurobiological correlates of these deficits complement our knowledge about their mutual relationships by showing that multiple neural networks are involved in the emergence of autism's signs and symptoms. Further investigation of various aspects of these cognitive deficits and the relationships between them may significantly improve our understanding of processes involved in the development of autism.
Sepsis induces apoptotic cell death in different regions of the brain in a rat model of sepsis
Authors: Kafa Ilker , Uysal Murat , Bakirci Sinan , Kurt M.
Published: November 2023

Sepsis occurs in 14-37 percent of patients admitted to intensive care units and sepsis associated encephalopathy (SAE) is its severe complication. In an attempt to provide insight into the question how sepsis and SAE contributes cerebral dysfunction, apoptotic cell death was investigated in hippocampal formation, centers of adult neurogenesis and main autonomic centers which are known to regulate heart rate, respiration and other visceral activities, in cecal ligation and puncture (CLP) rat model of sepsis. Vital parameters and electrophysiological changes were monitored for the confirmation of sepsis and SAE, respectively. Apoptotic cell death was evaluated by TUNEL staining, Caspase-3 immunohistochemistry and transmission electron microscope (TEM). Significantly higher number of TUNEL positive apoptotic cells in the median preoptic nucleus, subventricular zone, dentate gyrus and CA1 and CA3 regions of the hippocampal formation were observed in CLP group and Caspase-3 immunohistochemistry and TEM findings were in line with these results, suggesting that the apoptotic cell death would bare a major role in the pathogenesis of the SAE.
Lithium enhances cortical mRNA expression in ovariectomized C57BL/6J mice
Authors: Valdes James , Ramirez Franchesca , Juarez Barbara , Weeks Ophelia
Published: November 2023

The hippocampus and cortex of the mammalian brain are regions involved in learning and long-term memory. Estrogen and lithium affect similar learning and memory molecular processes. We hypothesized that in ovariectomized mice lithium treatment will enhance genetic factors in the brain that are involved in neuroprotection, learning and memory. Our study used bilaterally ovariectomized (bOVX) C57BL/6J mice treated for one month with 14.2 mM LiCl in their drinking water. Results indicate that LiCl-treated bOVX mice show enhanced cortical increases in mRNA expression of ER-alpha, NR1, Bcl-2, BDNF, and CaMkII-alpha; hippocampal mRNA showed no changes. Our results indicate that in bOVX C57BL/6J mice, lithium enhances the expression of specific cortical genes coded for proteins involved in learning, memory and neuroprotection.
Effects of chronic forced swim stress on hippocampal brain-derived neutrophic factor (BDNF) and its receptor (TrkB) immunoreactive cells in juvenile and aged rats
Authors: Badowska-Szalewska Ewa , Spodnik Edyta , Klejbor Ilona , Morys Janusz
Published: November 2023

A type of stress stimulation and age are claimed to affect the expression of brain-derived neurotrophic factor (BDNF) and its receptor – tyrosine kinase B (TrkB) in the hippocampal regions differentially. This study aimed to explore the influence of chronic (15 min daily for 21 days) forced swim stress (FS) exposure on the BDNF and TrkB containing neurons in the hippocampal CA1, CA3 pyramidal cell layers and dentate gyrus (DG) granule cell layer in juvenile (P28) and aged (P360) rats. An immunofluorescence (-ir) method was used to detect BDNF-ir and TrkB-ir cells. Under chronic FS exposure, in the group of juvenile rats a significant decrease in the density of BDNF immunoreactive neurons was observed in CA1 and DG (P less than
Proliferation capacity of cord blood derived neural stem cell line on different micro-scale biofunctional domains
Authors: Marzena  , Mehn Dora , Ruiz Ana , Colpo Pascal , Rossi Francois , Frontczak-Baniewicz Malgorzata , Domanska-Janik Krystyna , Buzanska Leonora
Published: November 2023

Physical interactions of cells with the adhesive substrates of the microenvironment as well as the presence of the soluble growth factors are important for the proliferation capacity of neural stem cells. We have used biofunctionalized surface domains microcontact printed with either synthetic polyaminoacid poly-L-lysine or extracellular matrix (ECM) component such as fibronectin, to study the proliferation capacity of human umbilical cord blood-derived neural stem cells (HUCB-NSC). The proliferation measured by the expression of Ki-67 protein was accompanied by the investigation of the cell morphology under the transmission and scanning electron microscopy in different culture time, plating densities of cells and medium condition (serum-free or 2 percent of FBS). The poly-L-lysine domains of defined micro-scale area promoted the presence of round, loosely attached Ki-67-positive cells, while fibronectin domains of the same size allowed appearance of flattened, strongly attached cells with more differentiated phenotype. These results were in agreement with the non-specific, electrostatic type of interaction between cell and substrate on poly-L-lysine and integrin receptor-mediated specific adhesion on fibronectin. In this report we have described in vitro culture conditions, which allow for immobilization of the non-differentiated and highly proliferating population of neural stem/progenitor cells to the biofunctionalized surface. The microarrays with bioactive domains allocating non-differentiated and proliferating neural stem/progenitor cells may find application for drug and chemicals toxicology screening of diverse factors influencing neural development.
Behavioral consequences of minimal traumatic brain injury in mice
Authors: Zohar Ofer , Rubovitch Vardit , Milman Anat , Schreiber Shaul , Pick Chaim
Published: November 2023

Victims of minor traumatic brain injury (mTBI), who show no clear morphological brain defects, frequently manifest cognitive, behavioral and emotional difficulties that can be long-lasting. In this paper we present a modified weight drop model used to deliver a closed head minimal traumatic brain injury to mice, which closely mimics real-life injuries and the symptoms observed in mTBI patients. Our choice of impact force does not produce structural damage to the brain and its surrounding tissue (as examined by MRI), any skull fracture, no edema and no evident damage to the blood-brain barrier (BBB). Moreover, our mTBI mice show no abnormal behavior on recovering from the weight drop, or any change in other brain functions such as reflexes, balance, exploration, strength, locomotor activity and swim speed. Since our mTBI model does not produce neurological, motor or sensory damage to the mice, it allows the direct evaluation of mTBI sequelae on the mice behavior and cognitive abilities. Using a variety of cognitive and behavioral tests (Morris water maze, staircase test, passive avoidance test, water T-maze, hot palate, elevated plus maze and forced swimming test) we assessed the short- and long-term sequelae induced by our model. Our results indicate that our closed head mTBI cause profound and long-lasting, irreversible learning and memory impairments, accompanied by a depressive-like behavior in mice that are evident even 90 days post injury. Our results indicate that the closed head mTBI model presented here may be useful in the development of novel therapeutic approaches, such as neuroprotective agents, for mTBI.
In vitro models of the blood-brain barrier
Authors: Wilhelm Imola , Fazakas Csilla , Krizbai Istvan
Published: November 2023

The blood-brain barrier (BBB) is an active interface between the circulation and the central nervous system (CNS) with a dual function: the barrier function restricts the transport from the blood to the brain of potentially toxic or harmful substances; the carrier function is responsible for the transport of nutrients to the brain and removal of metabolites. The BBB plays a crucial role in the clinical practice as well. On the one side there is a large number of neurological disorders including cerebral ischemia, brain trauma and tumors, neurodegenerative disorders, in which the permeability of the BBB is increased. On the other hand due to the relative impermeability of the barrier many drugs are unable to reach the CNS in therapeutically relevant concentration, making the BBB one of the major impediments in the treatment of CNS disorders. The significant scientific and industrial interest in the physiology and pathology of the BBB led to the development of several in vitro models of the BBB. These models are mainly based on the culture of cerebral endothelial cells. The best in vitro models which mimic the best way the in vivo anatomical conditions are the co-culture models in which brain endothelial cells are co-cultured with astrocytes and/or pericytes. Our in vitro BBB model is characterized by high transendothelial electrical resistance (TEER regularily above 200 Ohm times square cm), low permeability and expression of several transporters. Our experiments have proven that the model is suitable for basic research and for testing the interaction between the BBB and potential drug candidates (toxicity, permeability, interaction with efflux transporters) as well.
Chronic exposure to toluene changes the sleep-wake pattern and brain monoamine content in rats
Authors: Alfaro-Rodríguez Alfonso , Bueno-Nava Antonio , González-Piña Rigoberto , Arch-Tirado Emilio , Vargas-Sánchez Javier , Ávila-Luna Alberto
Published: November 2023

Toluene, found in glues and cleaners, is among the inhalants most commonly abused by workers and young drug addicts. In this study, we examined the changes in sleep patterns and monoamine content induced by chronic toluene exposure. Rats were chronically exposed to toluene vapors beginning at 30 days of age for a duration of 30 days. Experiment I was performed in a control group (n=10) and a chronic toluene exposure group (n=10). Rats were implanted with bipolar stainless steel electrodes for electroencephalographic recording (EEG). In experiment II, conducted in two other groups (control and exposed to toluene, n=10 each), animals were sacrificed by decapitation prior to chromatographic analysis. We found that chronic toluene administration affected the organization of sleep patterns and monoamine content. Dopamine (DA) and noradrenaline (NA) increased in the midbrain and striatum. 3,4-dihydroxyphenylacetic acid (DOPAC) increased only in the striatum. Midbrain levels of serotonin (5-HT) increased in the pons and decreased in the hypothalamus and striatum. 5-hydroxyindoleacetic acid (5-HIAA) increased in the pons, midbrain and striatum and decreased in the hypothalamus. Chronic toluene exposure induced changes in the serotonergic and dopaminergic systems and increased SWS and PS deficits. We conclude that toluene exposure disrupts the sleep-wake cycle by affecting the monoaminergic response in cerebral areas related to sleep.
Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade
Authors: Oyinbo Charles
Published: November 2023

The pathophysiology of acute spinal cord injury (SCI) involves primary and secondary mechanisms of injury. Though both mechanisms are involved in the neurological dysfunction in SCI most research however has focused on understanding the pathophysiology of the secondary damage and reducing the amount of delayed cell loss following SCI. Research has revealed extensive therapeutic windows in secondary injury mechanisms that could be manipulated by appropriate exogenous interventions. In contrast, primary injury to the cord happens unexpectedly, and it is associated with inevitable delays; ranging from several hours to days before care intervention is administered. Therefore, apart from achieving patient’s stabilization, the therapeutic window in the primary phase of injury is essentially obliterated, and consequently inaccessible for specialized. Coupled to this, the exacerbating effect of secondary injury mechanisms has generally commenced before the specialist intervention. Hence, knowledge of secondary injury mechanisms and their intricacies are invaluable requisite for any tailored therapeutic strategy in the persistent search for a cure of SCI. There are about 25 well-established secondary injury mechanisms in SCI, and are found in bits or clusters in literature. A vast number of these articles are not open access. Besides, articles with a comprehensive catalog of these mechanisms are not readily available. This article has cataloged over twenty five identified secondary mechanisms of injury in the spinal cord in an open access portal, and is particularly versatile for starters in spinal cord injury research.
Testosterone and its metabolites - modulators of brain functions
Authors: Durdiakova Jaroslava , Ostatnikova Daniela , Celec Peter
Published: November 2023

Testosterone is a steroid sex hormone with an important role in the physiology in both sexes. It is involved in the development of morphological and functional parameters of the body via multiple molecular mechanisms. Intensive research focused on testosterone reveals associations with cognitive abilities and behavior and its causative role in sex differences in cognition. Testosterone modulates brain structure and the differentiation of neurons during intrauterine development with profound effects on brain functions during postnatal life. In this review we summarize the effects of testosterone on brain physiology and cognition with respect to the underlying molecular mechanisms.
Direct MRI-guided stereotaxic viral mediated gene transfer of alpha-synuclein in the Gottingen minipig CNS
Authors: Glud,2 Andreas , Hedegaard Claus , Nielsen Mette , Sorensen Jens , Bendixen Christian , Jensen Poul , Mogensen Poul , Larsen Knud , Bjarkam,2 Carsten
Published: November 2023

The aim was to establish a non-primate large animal PD model by lentiviral vector mediated mutant alpha-synuclein overexpression in the substantia nigra. Lentivirus encoding A53T alpha-synuclein (6 x 2.5 microliter) was stereotaxically injected into the substantia nigra of six adult female Gottingen minipigs. Contralateral control injections encoding enhanced green fluorescent protein (EGFP) were performed. Gait-analysis was performed pre- and postoperatively. PCR of the transgenes and immunohistochemical staining against alpha-synuclein, EGFP, GFAP and TH was performed after 20 weeks. Gait analysis revealed a significant increase in step length and height, and a decrease in the double stand phase. PCR verified the mesencephalic presence of transgenes. IHC analysis showed alpha-synuclein expression in nigral neurons, around the injection tract and in related nigrostriatal projections. The alpha-synuclein positive neurons appeared swollen and vacuolated, in contrast to the EGFP-injected control side. To transduct all nigrostriatal cells with few microinjections, wider dissemination of the transgene must be achieved.
Lipopolysaccharide injected to pregnant mice affects behavior of their offspring in adulthood
Authors: Chlodzinska Natalia , Gajerska Monika , Bartkowska Katarzyna , Turlejski Kris , Djavadian Rouzanna
Published: November 2023

We studied consequences of maternal immune response on the course of pregnancy and the behavior of adult offspring. Mice in late gestation (day 16-17) were injected with lipopolysaccharide (LPS). Treatment of pregnant mice with high doses of LPS resulted in fetal resorption or stillbirths. Pregnant mice treated with low doses (100 or 300 micrograms/kg) of LPS gave birth to normal numbers of pups. However, behavior of the offspring was altered. Adult offspring of dams injected at a dose of 300 micrograms/kg of LPS traveled longer distances in the open field and spent more time in the central part of the arena, than mice in the control group. Female mice of this group spent more time in open arms of the elevated plus maze, in comparison to female control mice. Results of the Morris water maze test showed impairment of spatial learning and memory in male offspring born to LPS-injected dams. Furthermore, in the nest building test adult mice born from LPS challenged pregnancies constructed worse quality nests, which points to the presence of hippocampal dysfunction. These findings indicate that maternal bacterial infections during pregnancy may alter offspring behavior in adult life.
Neural generators of the auditory evoked potential components P3a and P3b
Authors: Wronka Eligiusz , Kaiser Jan , Coenen Anton
Published: November 2023

The aim of the present study was to define the scalp topography of the two subcomponents of the P3 component of the auditory evoked potential elicited in a three-stimulus oddball paradigm and to identify their cortical generators using the standardized low resolution electromagnetic tomography (sLORETA). Subjects were presented with a random sequence of auditory stimuli and instructed to respond to an infrequently occurring target stimulus inserted into a sequence of frequent standard and rare non-target stimuli. Results show that the magnitude of the frontal P3a is determined by the relative physical difference among stimuli, as it was larger for the stimulus more deviant from the standard. Major neural generators of the P3a were localized within frontal cortex and anterior cingulate gyrus. In contrast to this, the P3b, showing maximal amplitude at parietal locations, was larger for stimuli demanding a response than for the rare non-target. Major sources of the P3b included the superior parietal lobule and the posterior part of the cingulate gyrus. Our findings are in line with the hypothesis that P3a is related to alerting activity during the initial allocation of attention, while P3b is related to activation of a posterior network when the neuronal model of perceived stimulation is compared with the attentional trace.
Psychomotor and rewarding properties of the neurosteroids dehydroepiandrosterone sulphate and androsterone: Effects on monoamine and steroid metabolism
Authors: Zajda Malgorzata , Krzascik Pawel , Hill Martin , Majewska Maria
Published: November 2023

The neurosteroids, dehydroepiandrosterone sulfate (DHEAS) and androsterone, are implicated in drug addictions. We examined their influence on locomotor activity and reward in male Wistar rats, and on steroid and monoamine metabolism in the hippocampus and striatum. In the open field test, DHEAS injections (10, 40, 80 mg/kg, i.p.) 30 min prior the test had no significant effect on ambulation, but androsterone (10 mg/kg) increased general locomotion and at doses 1-10 mg/kg, increased central field activity, suggestive of an anxiolytic action. In the conditioned place preference test, both steroids had a biphasic effect: DHEAS was rewarding at doses of 10 and 40 mg/kg, but not at 80 mg/kg, while androsterone was rewarding at doses of 1 and 10 mg/kg, but aversive at 40 mg/kg. Monoamine and steroid concentrations were analyzed in homogenates from the hippocampus and striatum of DHEAS and androsterone injected rats. DHEAS reduced the hippocampal dopamine level, increased striatal homovanilic acid (HVA) and decreased the striatal serotonin concentrations. Androsterone did not affect dopamine levels or turnover, but increased noradrenaline concentration and serotonin turnover in the hippocampus. DHEAS administration augmented concentrations of DHEA, pregnenolone, androstendiol and androstentriol in both brain structures, while androsterone injections increased brain levels of androsterone, epiandrosterone, 5alpha-dihydrotestosterone, and androstandiol. Present data document that although psychobehavioral and neurochemical effects of DHEAS and androsterone differ in several aspects; both neurosteroids have rewarding properties at certain dose ranges, suggesting their likely involvement in addictions, which entail different mechanisms.
Determinants of filled/empty optical illusion: Differential effects of patterning
Authors: Wackermann Jiri
Published: November 2023

A subdivided path in the visual field appears longer than an empty path of the same length. This effect may be attributed to the division of the path into multiple segments, or to an influence of the visual elements used to mark the subdivision, and thus filling-up the estimated space. To address this question, we used two series of stimuli, in which the spatial distribution of the filling optical mater, or the form of the dividers, was varied while the relative coverage of the filled space was kept constant. We found significant dependence of the effect magnitude on a number of filling elements as well as on their form. These results indicate that the illusory space expansion is not merely an effect of 'filling-up' the space, but it also depends on the filling pattern. Consequences of these findings for the theory of the Oppel-Kundt phenomenon are briefly discussed.
Protective effect of treatment with black cumin oil on spatial cognitive functions of rats that suffered global cerebrovascular hypoperfusion
Authors: Azzubaidi Marwan , Saxena Anil , Talib Norlelawati , Ahmed Qamar , Dogarai Bashar
Published: November 2023

The fixed oil of black cumin seeds, Nigella sativa L. (NSO), has shown considerable antioxidant and anti-inflammatory activities. Chronic cerebral hypoperfusion has been linked to neurodegenerative disorders including Alzheimer's disease (AD) and its subsequent cognitive impairment in which oxidative stress and neuroinflammation are the principal culprits. Cerebrovascular hypoperfusion was experimentally achieved by bilateral common carotid arteries occlusion (2VO) in rats. Morris water maze (MWM) test was employed to assess the effects of NSO on spatial cognitive function before and after 2VO intervention. Rats were divided into long-term memory (LTM) and short-term memory (STM) groups, each was further subdivided into 3 subgroups: sham control, untreated 2VO and NSO treated 2VO group. All subgroups were tested with MWM at the tenth postoperative week. Working memory test results for both sham control and NSO treated groups showed significantly lower escape latency time and total distance travelled than untreated 2VO group. Similarly, LTM and STM MWM tests for sham control and NSO treated groups revealed significantly better maze test performance as compared to untreated 2VO group. Sham control and NSO treated 2VO groups demonstrated superior probe memory test performance as compared to untreated 2VO group. The fixed oil of Nigella sativa seeds has demonstrated noticeable spatial cognitive preservation in rats challenged with chronic cerebral hypoperfusion which indicates a promising prospective neuroprotective effect.
Influence of carbenoxolone on the anticonvulsant efficacy of phenytoin in pentylenetetrazole kindled rats
Authors: Sefil Fatih , Bagirici Faruk , Acar M. , Marangoz Cafer
Published: November 2023

Abnormal synchronized neuronal discharges mediated by gap junctions have an important role in epileptic seizures. The analysis of anticonvulsant drugs acting on gap junctions is still a priority in epilepsy research. Therefore, the present study was designed to investigate the effect of carbenoxolone, a gap junction blocker, on the anticonvulsant efficacy of phenytoin in pentylenetetrazole kindled rats. Male Wistar albino rats, 14 weeks of age, were used. In the first step of the study, animals were given PTZ 35 mg/kg intraperitoneally (i.p.) three times a week until kindling was produced. Then, indwelling screw electrodes - allowing EEG monitoring of conscious rats - were implanted into the crania of the kindled rats. In this way, we were able to record EEG activity and evaluate seizure stage at the same time. In the second step of the study, the interaction between carbenoxolone (40 mg/kg i.p.) and phenytoin (60 mg/kg, i.p.) was investigated. The data analysis was performed using a one-way ANOVA with LSD post-hoc test. Total spike number and the generalized seizure duration were reduced in the carbenoxolone treated group compared to the PTZ group. Phenytoin decreased generalized seizure duration, total spike number and seizure severity score. Carbenoxolone and phenytoin have anti-seizure effects in PTZ kindled rats. There was no significant difference between the carbenoxolone + phenytoin combination and phenytoin in terms of generalized seizure duration, total spike number and seizure stage. The results indicate that carbenoxolone combined with phenytoin is not more effective than the use of these drugs alone.
Region-related modular nerve-dependent motor activity in anorectum - cholinergic and nitrergic contribution to rat model
Authors: Stavreva Galya , Radomirov Radomir
Published: November 2023

Disturbances of enteric nerve-mediated anorectal evacuation mechanisms have medical and social impact. The study aimed at further eliciting the contribution of cholinergic and nitrergic neurotransmission systems to modular nerve networks in different regions of Wistar rat anorectum. Electrical field stimulation (EFS, 0.8 ms, 40 V, 2, 5 or 10 Hz, 20 s), computerized mechanographic on-line setup and drugs were used to evaluate the motor responses of isolated rings from circular muscle of rectum (proximal, middle, and distal part), internal anal sphincter, and anal canal. Twitch-like frequency-dependent contractions, more pronounced in rectal preparations, characterized the modular motor responses of rectal circular muscle rings and anal canal. Depending on the frequency of stimulation, the motor activity of internal anal sphincter varied from deep long-lasting relaxation to initial short-lasting relaxation, followed by a contraction. Electrically-evoked responses of anorectal preparations were tetrodotoxin (0.1 microM)-sensitive. In the presence of atropine (0.3 microM) the contractions of rectal rings decreased, relaxation of internal anal sphincter increased and inhibition of the contractions of the anal canal occurred, followed by relaxation. During atropine treatment, NG-nitro-L-arginine (0.5 microM) increased the contractile responses and suppressed internal anal sphincter relaxations. L-arginine (0.5 microM) decreased the contractions and extended the relaxations of internal anal sphincter and anal canal. Our results suggest that cholinergic and nitrergic systems are not equally involved in modular nerve networks of various regions of anorectum. Cholinergic transmission is more expressed in distal rectum, underlying its contractile potency, while nitric oxide-dependent transmission(s) control the relaxation ability of the internal anal sphincter and anal canal.
From otoacoustic emission to late auditory potentials P300: The inhibitory effect
Authors: Schochat Eliane , Matas Carla , Samelli Alessandra , Carvallo Renata
Published: November 2023

This study verifies the effects of contralateral noise on otoacoustic emissions and auditory evoked potentials. Short, middle and late auditory evoked potentials as well as otoacoustic emissions with and without white noise were assessed. Twenty-five subjects, normal-hearing, both genders, aged 18 to 30 years, were tested . In general, latencies of the various auditory potentials were increased at noise conditions, whereas amplitudes were diminished at noise conditions for short, middle and late latency responses combined in the same subject. The amplitude of otoacoustic emission decreased significantly in the condition with contralateral noise in comparison to the condition without noise. Our results indicate that most subjects presented different responses between conditions (with and without noise) in all tests, thereby suggesting that the efferent system was acting at both caudal and rostral portions of the auditory system.
Patterning of human cord blood-derived stem cells on single cell posts and lines: Implications for neural commitment
Authors: Zychowicz Marzena , Mehn Dora , Ruiz Ana , Frontczak-Baniewicz Malgorzata , Rossi Francois , Buzanska Leonora
Published: November 2023

Using stem cells (SC) in new strategies for clinical treatment requires control of stem cell fate decision and the ability to govern their patterning and commitment in tissue engineering. Neural stem cells and other adult SC can respond to the different components of the microenvironment and their spatial arrangement in the stem cell niche. It has been shown previously by our group that different composition and architecture of patterned bioactive domains influence the developmental response of neural stem cells. In the present report we verify the commitment and differentiation of neural stem cells derived from human cord blood (HUCB-NSC) by a single cell patterning system. Microcontact printing technology was used to generate single cell positioning areas of different geometry: 10 micrometer-thin lines and 10 micrometer-width one cell posts. The commitment and differentiation of HUCB-NSC cells cultured on different surfaces were dependent on the geometry and the type of biomaterial present in bioactive domains. Fibronectin promoted neuronal protrusion outgrowth (Beta-tubulin III and MAP-2 positive cells) and gap junction development (Cx43 marker) between cells growing on lines while poly-L-lysine promoted HUCB-NSC differentiation into astrocytic, glial fibrillary acidic protein expressing (GFAP positive) cell phenotype. Here we also demonstrate by scanning electron microscopy that morphology of cells on the patterned surface is highly dependent upon the type of biomolecules used for printing. These kinds of platforms can be used for investigating the influence of spatial organization of environment on the SC fate decision and for studying the molecular processes occurring in a single cell.
Restorative therapies to enhance sensorimotor recovery following cerebral ischemia
Authors: Ortega Francisco , Jolkkonen Jukka
Published: November 2023

The development of therapies that aim to facilitate functional recovery has identified potential approaches in stroke research. The main advantage of restorative therapies is their delayed administration after acute necrotic cell death, when the treatment can be combined with intensive rehabilitation and medication for poststroke complications to further enhance therapeutic benefit. Emerging understanding of brain repair and plasticity mechanisms after cerebral insults has revealed novel therapeutic targets including the promotion of axonal sprouting, altered perilesional GABA and glutamate receptor signaling, and enhancement of angiogenesis and endogenous neurogenesis. Interestingly, it seems that intensive rehabilitative training such as constraint-induced movement therapy also acts through these brain repair mechanisms, which may have an additive impact on functional recovery.
The role of zinc and copper in autism spectrum disorders
Authors: Bjorklund Geir
Published: November 2023

Autism spectrum disorders (ASDs) are a group of developmental disabilities that can cause significant social, communication and behavioral challenges. Several studies have suggested a disturbance in the copper (Cu) and zinc (Zn) metabolism in ASDs. Zinc deficiency, excess Cu levels, and low Zn/Cu ratio are common in children diagnosed with an ASD. The literature also suggests that mercury accumulation may occur as a cause or consequence of metallothionein (MT) dysfunction in children diagnosed with an ASD, which may be one of the causes of Zn deficiency. MTs are proteins with important functions in metal metabolism and protection. Zinc and Cu bind to and participate in the control of the synthesis of MT proteins. Studies indicate that the GABAergic system may be involved in ASDs, and that Zn and Cu may play a role in this system.
The number decision task: Investigation of the representation of multi-digit numbers
Authors: Sass Katharina , Theissen Lena , Munte Thomas , Habel Ute , Lugt Arie
Published: November 2023

The ability to process multi-digit numbers is an essential skill which we investigated using a number decision task. Subjects were asked to decide whether a target number (e.g., 649) is too small or too large to be the mean between two delimiter numbers that constituted the interval (e.g., 567 and 715). Three-digit numbers were presented vertically with (1) growing interval sizes (i.e., distance between the two delimiters; e.g., interval size between 567 and 715 is 148) and target gap to the mean (e.g., the gap between the ‘real’ mean 641 and the target 649 is 8) and (2) growing interval sizes with constant gap to the mean (i.e., for each interval size the gap between target and mean was held constant). The results showed that target gap to the mean “masked” the influence of interval sizes, i.e., subjects’ performance improved with increasing interval sizes (distance effect). This effect was reversed when constant target gaps to the mean and growing interval sizes were presented. These results were replicated presenting the numbers horizontally and with two-digit numbers. Additionally, a significant influence of decade but no effect of unit compatibility on reaction times and error rates, on number magnitude (size effect) and response format was found. Overall, we showed that the number decision task is an efficient tool to investigate multidigit number representation and the results from the experiments revealed evidence for a hybrid model of multi-digit number representation in which numbers are represented as a whole but also on separate mental number lines that interact with each other.
Cholinergic and nitrergic neuronal networks in the goldfish telencephalon
Authors: Giraldez-Perez Rosa , Gaytan Susana , Pasaro Rosario
Published: November 2023

The general organization of cholinergic and nitrergic elements in the central nervous system seems to be highly conserved among vertebrates, with the involvement of these neurotransmitter systems now well established in sensory, motor and cognitive processing. The goldfish is a widely used animal model in neuroanatomical, neurophysiological, and behavioral research. The purpose of this study was to examine pallial and subpallial cholinoceptive, cholinergic and nitrergic populations in the goldfish telencephalon by means of histochemical and immunohistochemical techniques in order to identify neurons containing acetylcholinesterase (AChE), choline acetyltransferase (ChAT), NADPH-diaphorase (NADPHd), and neuronal nitric oxide synthase (nNOS), and to relate their distribution to their putative functional significance. Regions containing AChE-labeled neurons represented terminal fields of cholinergic inputs as well as a widespread distribution of AChE-related enzymes; these regions also usually contained NADPHd-labeled neurons and often contained small numbers of nNOS-positive cells. However, the ventral subdivisions of the medial and lateral parts of the dorsal telencephalic area, and the ventral and lateral parts of the ventral telencephalic area, were devoid of nNOS-labeled cells. ChAT-positive neurons were found only in the lateral part of the ventral telencephalic area. ChAT- and nNOS-positive fibers exhibited a radial orientation, and were seen as thin axons with en-passant boutons. The distribution of these elements could help to elucidate the role of cholinergic and nitrergic neuronal networks in the goldfish telencephalon.
Long-term effects of the maternal deprivation on the volume and number of neurons in the rat neocortex and hippocampus
Authors: Aksic Milan , Radonjic Nevena , Aleksic Dubravka , Jevtic Gordana , Markovic Branka , Petronijevic Natasa , Radonjic Vidosava , Filipovic Branislav
Published: November 2023

Maternal deprivation (MD) leads to a variety of behavioral changes in rats which closely resemble the symptoms of schizophrenia in humans. With the aim to investigate the morphological changes which underlie the behavioral insults in this experimental paradigm we exposed 9-day-old Wistar rats to a 24 h MD. At the period of young adulthood rats were sacrificed for morphometric analysis and their brains were compared to the control group. Rats exposed to MD had a decrease in hippocampal volume (71 percent of the control value) as well as a decrease in the size of pyramidal (62 percent of the control) and granular (60 percent of the control) cell layers. Also, there was a decrease in the thickness of the prefrontal, retrosplenial and motor cortex compared to the control group. Analysis of the density of NeuN-immunolabeled neurons revealed a reduction in retrosplenial and prefrontal cortex (70 percent and 81 percent of the control, respectively), while there was no difference in the motor cortex. Western blot analysis confirmed a decrease in NeuN expression in the MD group compared to the control rat brain homogenates. The results of this study show that early stress in life has a long-term effect on the morphology of cognitive brain regions, most probably due to the loss of neurons during postnatal development and further contributes to our understanding of the effects of maternal separation on brain development.
Lesions of the lateral entorhinal cortex disrupt non-spatial latent learning but spare spatial latent learning in the rat (Rattus norvegicus)
Authors: Stouffer Eric , Klein Jessalyn
Published: November 2023

The current study examined the function of the lateral entorhinal cortex (LEC) in a non-spatial latent learning task and a spatial latent learning task. Latent learning is the acquisition of neutral information that does not immediately influence behavior, but can be recalled and utilized when it becomes relevant to the animal. Based on previous research, it was predicted that the LEC would be necessary for latent learning of non-spatial information, but would not be necessary for latent learning of spatial information. Forty-two male Sprague Dawley rats (Rattus norvegicus) were either given pretraining neurotoxic lesions restricted to the LEC or were given sham (SH) lesions. The rats were then trained and tested on two latent learning tasks: the Latent Cue Preference (LCP) task which assesses single-cue (non-spatial) latent learning and a spatial latent learning task utilizing a Barnes maze. Results showed that rats with LEC lesions were impaired on the nonspatial LCP task compared to SH rats, but showed no impairment on the spatial latent learning task. Therefore, the LEC appears to be selectively involved in processing non-spatial latent learning and does not process, or is at least not necessary for, spatial latent learning. These findings indicate a specific role of the LEC in information processing and provide new information about the function of the entorhinal cortex.
Animal models of schizophrenia: Developmental preparation in rats
Authors: Ratajczak Piotr , Wozniak Anna , Nowakowska Elzbieta
Published: November 2023

Schizophrenia manifests itself primarily with positive symptoms, negative symptoms and cognitive disorders. Animal models of mental diseases seem to be an important tool in understanding key theories related with pathophysiology of the disorder and are used to assess efficacy of new drugs. References describe four basic groups of animal models of schizophrenia, such as: models created by pharmacological intervention, genetic models, lesion models and models of developmental disorders of primary brain structures. Of the models referred to above, the group of developmental disorder models is particularly noteworthy, as they are primarily easy to use, and the methods are highly sensitive. High scientific value of these models is associated with the neurodevelopmental theory which stipulates that at an early stage of body development, a number of interactions between genetic and environmental factors may affect the development of neurons which may cause disorders of brain cytoarchitecture development. We review six developmental models of schizophrenia in rats (MAM – methylooxymethanol acetate, prenatal stress, maternal deprivation, isolation rearing, prenatal immune challenge and maternal malnutrition) that are all validated by disruption in PPI.
Porous tantalum and tantalum oxide nanoparticles for regenerative medicine
Authors: Mohandas Gokhuldass , Oskolkov Nikita , McMahon Michael , Walczak Piotr , Janowski Miroslaw
Published: November 2023

For centuries, inflammatory/foreign body reactions have plagued the attempts of clinicians to use metals for tissue and bone reconstructions. Since corrosion contributes to the rejection of metal by the body, an extremely bioinert metal – tantalum – has been successfully used in medicine. The outstanding biocompatibility and flexibility of tantalum established the basis for a growing cadre of clinical applications. One important application which benefited from the introduction of powder (particle) metallurgy is use of tantalum as bone implants. Porous materials have re-shaped the landscape of bone implants, as they allow for bone ingrowth and biological fixation, and eliminate implant loosening and related treatment failures. The unique bone-mimicking properties of porous tantalum enabled the use of tantalum as a material for bulk implants, and not only for coatings, as is the case with other porous metals. Moreover, porous tantalum also facilitates the ingrowth of soft tissue, including the formation of blood vessels that were found to assemble on the surface and within the structure of the porous tantalum. Also, since tantalum is strongly radiopaque due its high atomic number, this property is widely employed for marking in orthopedics and in endovascular medical devices. Another important development was the production of nanoparticles based on tantalum. These particles have been shown to be superior to iodinated contrast agents for blood pool imaging applications due to their longer circulation time. Their properties are similar to gold nanoparticles, but are far more cost-effective, and thus, well-positioned to replace gold in regenerative medicine for labeling and tracking of cell grafts through x-ray-based imaging. However, the amount of tantalum nanoparticles that can be taken up by stem cells is not enough to make individual cells visible in x-ray images. Thus, alternative strategies are needed, such as hydrogel or nanofiber scaffolds, which can be loaded with higher concentrations of nanoparticles, to increase the precision of cell deposition and allow tracking under x-ray guidance.
Cerebral cortical hypoplasia with abnormal morphology of pyramidal neuron in growth-retarded mouse (grt/grt)
Authors: Horiuchi-Hirose Miwa , Saito Shigeyoshi , Sato Chika , Aoyama Junya , Kobayashi Tetsuya , Sawada Kazuhiko
Published: November 2023

The purpose of this study was to quantitatively characterize structural abnormalities of the cerebrum in a growth-retarded mouse (grt/grt) with a tyrosylprotein sulfotransferase 2 gene defect. Three-dimensional computed tomography (CT) images were obtained from fixed brains of male homogenous grt/grt (n=5) and heterozygous grt/+ (n=5) mice at 15 weeks of age, and volumes of representative cerebral regions were calculated on the basis of those images. Following CT measurements, cryosections of the brain were made, and immunohistochemistry for NeuN and SMI-32 was carried out. By CT-based volumetry, region-specific reductions in volumes were marked in the cerebral cortex and white matter, but not in other cerebral regions of grt/grt. When quantitatively evaluating the shape of the cerebral cortex, the frontooccipital length of the cortex was significantly smaller in grt/grt than in grt/+, whereas the cortical width was not altered in grt/grt. On the other hand, both cortical thickness and density of NeuN-immunopositive neurons in three distinctive cortical regions, i.e., the primary motor cortex, barrel field of primary somatosensory cortex and primary visual cortex, were not different between grt/grt and grt/+. By semi-quantitative immunohistochemical analysis, the intensity of SMI-32 immunostaining was significantly weaker in grt/grt than in grt/+ in the three cortical areas examined. SMI-32 staining was reduced, particularly in layer III pyramidal neurons in grt/grt, while it was sustained in multipolar neurons. The present results suggest that cerebral abnormalities in grt/grt mice are characterized by cortical hypoplasia at the frontooccipital axis with immature pyramidal neurons and insufficient development of callosal fibers.
Systemic inflammation induces a profound long term brain cell injury in rats
Authors: Fan Long , Wang Tianlong , Chang Lirong , Song Yizhi , Wu Yan , Ma Daqing
Published: November 2023

The long term impact of neuroflammation induced by systemic inflammation on astroglial transcription factor nuclear factor (NF)-kappaB activation in the sub-region of hippocampus as well as its’ association with the ultra-structural changes in brain cells are yet unknow. In this study, rats received 10 mg/kg of lipopolysaccharide (LPS, ip injection) and NF-kappaBp65 expression on the astroglia as well as the neuronal and astroglial ultra-structural changes and/or death and microvasculature damage were assessed with immunofluorescence and transmission electron microscopy respectively up to 16 days after treatment. The results showed that in the CA1 and CA3 region of the hippocampus, the fluorescence intensity of NF-kappaBp65 was increased from day 1 after LPS injection, reaching a peak at day 3, and stayed at higher level when compared to the control up to 16 days after LPS treatment (P
Reprogramming of somatic cells: possible methods to derive safe, clinical-grade human induced pluripotent stem cells
Authors: Augustyniak Justyna , Zychowicz Marzena , Podobinska Martyna , Barta Tomas , Buzanska Leonora
Published: November 2023

Derivation of pluripotent stem cells from adult somatic tissues by reprogramming technology has opened new therapeutic possibilities. Current most efficient procedures for derivation of induced pluripotent stem (iPS) cells are based on the viral vectors, which represent the danger of insertional mutagenesis during incorporation of introduced genes into the host genome. To circumvent this problem, the new, safe, non-integrative and non-viral strategies of reprogramming have been developed. In this review we discuss novel DNA-free and viral-free methods of reprogramming to iPS cells including protein transduction, mRNA and microRNA delivery.
Single course of antenatal betamethasone produces delayed changes in morphology and calbindin-D28k expression in a rat’s cerebellar Purkinje cells
Authors: Pascual Rodrigo , Valencia Martina , Larrea Sebastian , Bustamante Carlos
Published: November 2023

In the current study, we analyzed the impact of antenatal betamethasone on macroscopic cerebellar development, Purkinje cell morphology and the expression of the neuroprotective protein calbindin-D28k. Pregnant rats (Sprague-Dawley) were randomly divided into two experimental groups: control (CONT) and betamethasone-treated (BET). At gestational day 20 (G20), BET dams were subcutaneously injected with a solution of 0.17 mg kg-1 of betamethasone, while CONT animals received a similar volume of saline. At postnatal days 22 (P22) and P52, BET and CONT offspring were behaviorally evaluated, and the cerebella were histologically and immunohistochemically processed. Animals that were prenatally treated with a single course of betamethasone exhibited long-lasting behavioral changes consistent with anxiety-like behavior in the open-field test, together with (1) reduced cerebellar weight and volume, (2) Purkinje cell dendritic atrophy, and (3) an overexpression of calbindin-D28k. The current results indicate that an experimental single course of betamethasone in pregnant rats produces long-lasting anxiety-like behaviors, together with macroscopic and microscopic cerebellar alterations.