Opera Medica et Physiologica

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Supplement S 1 | September 2017

Symposium
Published ahead of print September 13, 2017; Printed September 15, 2017; OM&P 2017 Volume 3 Supplement S 1, pages 1-15
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volume 3 suplement s1.pdf730.75 KB
Published ahead of print September 13, 2017; Printed September 15, 2017; OM&P 2017 Volume 3 Supplement S 1, pages 16
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author index.pdf137 KB

Issue 2 | June 2017

Published ahead of print July 16, 2017; Printed June 30, 2017; OM&P 2017 Volume 3 Issue 2, pages 48-58; doi:10.20388/omp2017.002.0045
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The rapid advance of super-resolution microscopy and its experimental applications has provided neuroscientists with a pass to the nanoscopic world of synaptic machinery. Here we will briefly overview and discuss current progress in our understanding of the three-dimensional synaptic architecture and molecular organisation as gleaned from the imaging methods that go beyond the diffraction limit of conventional light microscopy. We will argue that such methods are to take our knowledge of synapses to a qualitatively new level, providing the neuroscience research community with novel organising principles and concepts pertinent to the workings of the brain. 


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OMP_2017_02_0045.pdf878.89 KB
Published ahead of print June 19, 2017; Printed June 30, 2017; OM&P 2017 Volume 3 Issue 2, pages 39-47; doi:10.20388/omp2017.002.0047
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The aim of the present study was to explore the effects of 8-OH-DPAT, 5-HT1A receptor agonist and NAN-190, 5-HT1A receptor antagonist on anxiety-related behavior in the adult gonadectomized (GDX) male rats. Moreover, another goal of this work was to investigate whether the combination of 8-OH-DPAT or NAN-190 plus testosterone propionate (TP) could affect anxiety-like behavior more than TP alone in the adult GDX rats. Two weeks after gonadectomy, GDX rats were subjected by treatments with the solvent, TP (0.5 mg/kg, s.c.), 8-OH-DPAT (0.05 mg/kg, s.c.), NAN-190 (0.1 mg/kg, i.p.), 8-OH-DPAT in a combination with TP or NAN-190 in a combination with TP during 14 days. Experimental groups of GDX rats and control group of intact males were then tested in the elevated plus maze (EPM) and the open field test. 8-OH-DPAT treatment failed to modify anxiety-like behavior of GDX rats in the EPM as compared to the GDX rats given with oil solvent. NAN-190 injected alone or in combination with TP to GDX rats resulted in a significant anxiolytic-like effect as compared to the GDX given with oil solvent or TP application. Our data indicate that the combination of NAN-190 and TP is more effective than TP alone in GDX rats inducing a more profound anxiolytic-like effect in the EPM. Thus, the results of this study suggest that effects of 5-HT1A receptor agonist/antagonist can modify anxiety level in opposite direction in male rats after gonadectomy.


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OMP_2017_02_0047.pdf400.38 KB
Published ahead of print June 18, 2017; Printed June 30, 2017; OM&P 2017 Volume 3 Issue 2, pages 31-38; doi:10.20388/omp2017.002.0046
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Nitric oxide (NO) signalling contributes to many biological processes involved in activity-dependent fine tuning of neuronal communication. NO is involved in early developmental signalling of the nervous system and is associated with pathological pathways and age-related decline in neuronal function, thus playing a critical role in regulating neuronal function in physiology and disease. Here we assessed the effects of modulating endogenous neuronal nitric oxide synthase (NOS) activity on synaptic function, specifically on neurotransmitter release at the glutamatergic Drosophila neuromuscular junction (NMJ). We found that the absence of NOS activity enhanced synaptic release at the NMJ and conversely, overexpression of NOS diminished transmitter release. The effects of alterations in NO signalling are the consequence of acute signalling at the synapse as we did not observe any developmental changes in NMJ morphology or synaptic parameters, such as expression of the active zone protein, bruchpilot, which could account for changes in release. Ultrastructural analysis did not show any developmental effects in boutons from larvae with reduced NOS activity. Together, our data present evidence for a negative regulation of transmitter release by NO which has implications for physiological synaptic function but also pathological and age-related dysregulation of synaptic signalling. 

 


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OMP_2017_02_0046.pdf3.06 MB

Issue 1 | March 2017

Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 1-13; doi:10.20388/omp2017.001.0041
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The role of chaos in biological information processing has been established as an  important breakthrough of nonlinear dynamics, after the early pioneering work of J.S. Nicolis and notably in neuroscience by the work of Walter J. Freeman and co-workers spanning more than three decades.  In this work we revisit the subject and we further focus on novel results that reveal its underlying logical  structure when  faced with the cognition of ambiguous stimuli. We demonstrate, by utilizing a minimal model for apprehension and judgement related to Bayesian updating,  that the fundamental characteristics of a biological processor obey in this case an extended, non-Boolean, logic which is characterized as  a quantum logic. And we realize that in its essence the role of chaos in biological information processing accounts for, and is fully compatible with, the logic of “quantum cognition” in psychology and neuroscience.


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OMP_2017_01_0041.pdf1.37 MB
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 19-24; doi:10.20388/omp2017.001.0042
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Understanding the molecular and cellular processes that cause dementia is one of the most important challenges in neuroscience. SUMOylation is a post-translational protein modification that has been strongly implicated in neurodegenerative diseases. To investigate SUMOylation in dementia we profiled the expression of key SUMOylation pathway proteins in post mortem brain tissue from Alzheimer’s Disease (AD) and Down’s Syndrome (DS) patients. As expected, both AD and DS tissue displayed massively increased levels of phosphorylated tau compared to age- and sex-matched controls. Surprisingly, there were no changes in the levels of the E1 and E2 enzymes required for protein SUMOylation, or in levels of the deSUMOylating enzyme SENP1.  There was, however, a marked decrease in the SUMO-2/3-specific deSUMOylating enzyme SENP3 in DS. There were also increased levels of SUMO-1 conjugated proteins in DS, but not in AD tissue. While these results do not exclude roles for SUMOylation in AD, they demonstrate clear differences in the profile of SUMOylation and in the expression of deSUMOylating enzymes between AD and DS brain.


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OMP_2017_01_0042.pdf693.98 KB
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 25-29; doi:10.20388/omp2017.001.0044
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Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal system, affecting adults and children. Its cause is unknown, and the knowledge of reliable biomarkers is limited, especially for children. That makes the search for new biomarkers and pushing forth the analysis of the available data particularly challenging. We investigate proteomic data from children patients as a promising source, and tackle the problem implementing the recently developed parenclitic network approach to machine learning algorithms that solve classification task for proteomic data from healthy and diseased. We expect our approach to be applicable to other gastrointestinal diseases.


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OMP_2017_001_0044.pdf1.15 MB
Published ahead of print March 29, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 14-18; doi:10.20388/omp2017.001.0043
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A spatially stable pattern of two coexisting coherent and incoherent subpopulations in nonlocally coupled dynamical systems is called as chimera states and seen in many paradigmatic limit cycle as well as chaotic models where the coupling interaction is basically diffusive type. In neuronal networks, besides diffusive electrotonic communication via gap junctions, chemical transmission occurs between the pre-synapse and post-synapse of neurons. We consider, in a numerical study, a network of neurons in a ring using the Hindmarsh-Rose (HR) bursting model for each node of the network and, apply attractive gap junctions for local coupling between the nearest neighbors and inhibitory nonlocal coupling via chemical synaptic transmission between the distant neighbors. For a range of gap junctional and chemical synaptic coupling strengths, a subpopulation of the neuronal network, in the ring, bursts asynchronously and another subpopulation remains silent in a synchronous state. The bursting subpopulation of neurons fires sequentially along the ring when the number of firing nodes remains same but change their positions periodically in time. It appears as a traveling chimera pattern in the ring when the dynamics of the individual bursting nodes is chaotic. The chimera pattern travels in a reverse direction for a larger chemical synaptic coupling strength. A purely inhibitory chemical synaptic coupling can produce a similar traveling chimera pattern, however, the dynamics of the firing nodes is then periodic.

 


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OMP_2017_001_0043.pdf1.12 MB

Issue 3, 4 | December 2016

Published ahead of print December 20, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, 4, pages 173-176; doi:10.20388/omp2016.003.0036
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Given the recent findings on the importance of CD38 signaling in the pathogenesis of colon cancer. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. CD38 has a genetic polymorphism, characterized by a C>G variation in the regulatory region of intron 1. The working hypothesis is that the presence of different alleles in colon cancer patients accounts for some of the clinical heterogeneity. CD38 is considered a marker of prognosis and as an indicator the activation and proliferation of cells. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. We evaluated one potentially functional CD38 SNP, intronic rs6449182 in two cases patients and controls. Genotyping was done using PCR-based assays in a total of 93 patients with colon cancer and 100 controls. We found that frequencies of variant allele (rs6449182 G) were significantly higher in colon cancer. Logistic regression analysis revealed an association between colon cancer and genotypes: rs6449182 CC [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.32 – 1.01], rs6449182 CG (OR, 1.47; 95% CI, 0.83 – 2.60), and rs6449182 GG (OR, 2.26; 95% CI, 0.66 – 7.77). We observed that rs6449182 G carriers had more advanced clinical stage (P = 0.04). In conclusion, our data show that CD38 SNP may affect CD38 expression and contribute to the increased risk of colon cancer carcinogenesis.


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OMP_2016_03_0036.pdf310.92 KB
Published ahead of print December 19, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, 4, pages 177-180; doi:10.20388/omp2016.003.0037
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The assembly of neural circuits during development endows the brain with the ability to perceive the environment, control motor output, and perform higher cognitive functions. Failure to assemble proper neural circuits may result in neurodevelopmental disorders including intellectual disability and autism spectrum disorders. Epigenetic mechanisms, and in particular chromatin remodeling, are potent regulators of neuronal connectivity. Here, we review recent studies highlighting the essential role of the ATPdependent nucleosomal remodeling and deacetylase (NuRD) complex in epigenetic programming of neurons to drive neural circuit assembly and organism behavior. 


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OMP_2016_03_0037.pdf499.46 KB
Published ahead of print December 18, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, 4, pages 181-187; doi:10.20388/omp2016.003.0040
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Isolated brain tumors contain cells that exhibit stem cell features and a tissue microenvironment bearing remarkable similarities to the normal neurogenic niche. This supports the idea that neural stem (NSCs) or progenitor cells, and their progeny are the likely tumor cell(s) of origin. This prompted the investigation of the relationship between NSCs/progenitors and the initiation of tumorigenesis. These studies led to the identification of common signaling machineries underlying NSC development and tumor formation, particularly those with known roles in proliferation and cell fate determination. This review will explore the molecular mechanisms that regulate NSC behavior in the neurogenic niche of the forebrain, and how deregulation of the developmental potential of NSCs might contribute to tumorigenesis. 


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OMP_2016_03_0040.pdf1.56 MB
Published ahead of print December 17, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, 4, pages 188-204; doi:10.20388/OMP.003.0034
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Neurons adapt to stimuli through activity dependent changes to their transcriptome, a process mediated by immediate-early gene networks.  Recent findings that transcriptional activation of neuronal immediate-early genes requires the formation of controlled DNA double-strand breaks (DSBs) has come as a surprise and has profound implications for neuronal function, especially in the aging brain.  Here we review recent literature surrounding the phenomena of activity-dependent DNA DSBs in neurons and how this process may be exploited by transposable elements (TEs) in both naïve and aging neurons.  We hypothesize the existence of Activity DEPendent Transposition (ADEPT), where neuronal excitation is able to induce genomic rearrangements through either de novo integration of TEs or by homology-directed recombination of TE-derived repetitive sequences.  Epigenetic drift may cause the magnitude of ADEPT to increase with age, leading to genome instability, which we suggest presages most, if not all, neurodegenerative diseases.


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OMP_2016_03_0034.pdf2.84 MB
Published ahead of print December 16, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, 4, pages 205-210; doi:10.20388/omp2016.003.0039
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The presynaptic modifications that accompany long-term changes in synaptic plasticity are still not fully understood. Synaptophysin is a major synaptic vesicle protein involved in neurotransmitter release. We have used quantitative electron microscopy to study synaptophysin (Syn) immunolabelling in the hippocampus of adult rats 24h after induction in vivo of long term potentiation (LTP), and long term depression (LTD). Electrodes were implanted chronically in hippocampus with stimulation at either the medial (MPP) or lateral perforant path (LPP). 24h following induction of LTP or LTD rats were rapidly perfusion fixed and hippocampal tissue processed to electron microscopy via freeze substitution method. Anti-synaptophysin post-embedding immunolabelling was performed and tissue was imaged in the middle molecular layer (MML) of the dentate gyrus. There was a significant decrease in number of Syn labelled vesicles per unit area of bouton after LTP, but not LTD. An analysis of the spatial distribution of Syn labelled synaptic vesicles showed an increase in nearest neighbour distances, more so in the LTP than the LTD group, which is consistent with the overall decrease of Syn after LTP. These data are in agreement with the suggestion that Syn is involved in clathrin-dependent and “kiss and run” endocytosis which occurs perisynaptically. Thus, an increase in release of neurotransmitter and in consequence endocytosis would be consistent with an increased active zone distance for vesicles containing Syn.


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OMP_2016_03_0039.pdf729.3 KB
Published ahead of print December 15, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, 4, pages 211-227; doi:10.20388/ OMP.003.0035
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Neural prostheses (NPs) link the brain to external devices, with an eventual goal of recovery of motor and sensory functions to patients with neurological conditions. Over the past half-century, NPs have advanced significantly from the early ideas that sounded like science fiction to the modern high-tech implementations. In particular, invasive recordings using multichannel implants have enabled real-time control of artificial limbs by nonhuman primates and human subjects. Furthermore, NPs can provide artificial sensory feedback, allowing users to perceive the movements of prosthetic limbs and their haptic interaction with external objects. Recently, NP approach was used to build brain-nets that enable information exchange between individual brains and execution of cooperative tasks. This review focuses on invasive NPs for sensorimotor functions.


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OMP_2016_03_0035.pdf658.45 KB
Published ahead of print December 14, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, 4, pages 228-234; doi:10.20388/omp2016.003.0038
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We revisit the Wendling-Chauvel neural mass model by reducing it to eight ODEs and adding a dierential equation that accounts for a dynamic evolution of the slow inhibitory synaptic gain. This allows to generate dynamic transitions in the resulting nine-dimensional model. The output of the extended model can be related to EEG patterns observed during epileptic seizure, in particular isolated pre-ictal spikes and low-voltage fast oscillations at seizure onset. We analyse the extended model using basic tools from slow-fast dynamical systems theory and relate the main transitions towards seizure states to torus canards, a type of solutions that has been shown to explain the spiking to bursting transition in many neural models. We nd that the original ten-dimensional Wendling-Chauvel model can be reduced to eight dimensions, two variables being scaled versions of two other variables of the model. We then obtain a model with four PSP blocks, which is consistent with the block-diagrams typically presented to describe this model. Instead of varying the slow inhibitory synaptic gain parameter B quasi-statically, or just performing numerical bifurcation analysis in B as the structure of the fast subsystem of an hypothetical extended system, we construct a true slow dynamics for B, depending sensitively on the main PSP output of the model, Y0. Near fold bifurcation of limit cycles of the original model, the solution to the extended model performs fast low-amplitude oscillations close to both attracting and repelling branches of limit cycles, which is the signature of a torus canard phenomenon.


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Issue 2 | July 2016

Published ahead of print July 10, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 87-102; doi:10.20388/OMP2016.002.0026
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Glycogen synthase kinase 3 (GSK-3) is an important molecular player involved into diverse cellular functions including metabolism, transcription, cell survival and synaptic plasticity. Here, we focused on characterization of the cognitive effects of GSK-3 inhibitor, a newly developed compound VP3.36. In particular, we assessed VP3.36 effects on working memory, episodic memory, executive functioning, spatial learning & memory and fear memory. VP3.36 (3 mg/kg) significantly enhanced working memory and spatial object recognition in C57BL/6J mice. The GSK-3 inhibitor was able to speed up solving obstacles given to experimental animals in the Puzzle test, thereby improving their executive functions. Lastly, VP3.36-treated mice learnt faster to find the escape platform in the Morris’ water maze and exhibited better spatial long-term memory than vehicle-treated animals. At the same time, GSK-3 inhibition did not affect fear memories, sensorimotor gating, emotional behavior or ambulation, suggesting that GSK-3 inhibition underlies specific cognitive processes, which are likely coupled with certain mechanisms of synaptic plasticity. Given that GSK-3 inhibition has clear effect on long-term depression (LTD), and the functional role of LTD in brain is still far from complete understanding, next, we probed effects of VP3.36 on synaptic LTD in the hippocampal CA1 subregion. We found that incubation of hippocampal slices with VP3.36 sufficiently prevented synaptic LTD, further supporting implication of GSK-3 into mechanisms of synaptic plasticity. Taken together, VP3.36 facilitated working memory, spatial episodic and long-term memory, enhanced executive functions in parallel with its ability to prevent synaptic LTD. Overall, our experiments showed implication of GSK-3 into mechanisms of synaptic plasticity and certain cognitive functions which help to deeper understand fundamental molecular-cellular mechanisms of cognitive enhancement’s processes. 


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OMP_2016_04_0026.pdf575.02 KB
Published ahead of print July 09, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 103-111; doi:10.20388/OMP2016.002.0027
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Matrix metalloproteinase 9, MMP-9 is an extracellularly operating enzyme that has been demonstrated as an important regulatory molecule in control of synaptic plasticity, learning and memory. Either genetic or pharmacological inhibition of MMP-9 impairs late phase of long-term potentiation at various pathways, as well as appetitive and spatial memory formation, although aversive learning remains apparently intact in MMP-9 KO mice. MMP-9 is locally translated and released from the excitatory synapses in response to neuronal activity. Extrasynaptic MMP-9 is required for growth and maturation of the dendritic spines to accumulate and immobilize AMPA receptors, making the excitatory synapses more efficacious. Animal studies have implicated MMP-9 in such neuropsychiatric conditions, as e.g., epileptogenesis, autism spectrum disorders, development of addiction, and depression. In humans, MMP-9 appears to contribute to epilepsy, alcohol addiction, Fragile X Syndrome, schizophrenia and bipolar disorder. In aggregate, all those conditions may be considered as relying on alterations of dendritic spines/excitatory synapses and thus understanding the role played by MMP-9 in the synaptic plasticity may allow to elucidate the underpinnings of major neuropsychiatric disorders.


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OMP_2016_04_0027.pdf352.98 KB
Published ahead of print July 08, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 112-116; doi:10.20388/OMP2016.002.0033
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We propose a new approach for the quantitative characterization of cognitive human brain activity during visual perception. According to the theoretical background we analyze human electro-encephalograms (EEG) obtained while the subjects observe ambiguous images. We found that the decision-making process is characterized by specific oscillatory patterns in the multi-channel EEG data.


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OMP_2016_02_0033.pdf1.47 MB
Published ahead of print July 07, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 117-121; doi:10.20388/OMP2016.002.0032
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This review focuses on general optogenetics issues (in particular the choice of the necessary light exposure settings), as well as certain promising areas of research with optogenetics.


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OMP_2016_02_0032.pdf332.06 KB
Published ahead of print July 06, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 122-140; doi:10.20388/OMP2016.002.0029
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Astrocytes perform fundamental housekeeping functions in the central nervous system and through bidirectional communication with neurons are thought to coordinate synaptic transmission and plasticity. They are also renowned actors in brain pathology. Reactive gliosis and neuroinflammation are featured by many (if not all) acute and chronic neurodegenerative pathologies including Alzheimer’s disease (AD). The Ca2+/calmodulin-activated phosphatase calcineurin (CaN) plays a central role in the pathology-related changes of astroglial cells mainly through activation of the inflammation-related transcription factors Nuclear Factor of Activated T-cells (NFAT) and Nuclear Factor kB (NF-kB). In this contribution we focus on the mechanistic aspects of CaN signalling in astrocytes. We analyze the astroglial Ca2+ signalling toolkit in the context of Ca2+ signals necessary for CaN activation and focus on the astroglial CaN signalling through its direct target, NFAT, as well as the intricate relationships between CaN and NF-kB activation pathways.The majority of data about CaN-mediated signalling in astrocytes point to the role for CaN in pathology-related conditions while very little is currently known about signalling and function of astroglial CaN in physiology.


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OMP_2016_02_0029.pdf1.07 MB
Published ahead of print July 05, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 141-152; doi:10.20388/OMP2016.002.0028
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Maintenance of genome stability in the face of DNA damage is essential for cellular homeostasis and prevention of cancer and brain degeneration. The DNA damage response (DDR) is a complex response that is rapidly activated when a DNA lesion occurs in chromosomal DNA. Mutations affecting the proteins involved in the DDR can lead to genomic instability syndromes that involve tissue degeneration, cancer predisposition, premature aging, and brain mal-development and degeneration. Mutation of the kinase ATM leads to a prototype genomic instability syndrome, ataxia-telangiectasia (A-T). A-T is characterized by progressive cerebellar degeneration, immunodeficiency, genome instability, premature aging, gonadal dysgenesis, extreme radiosensitivity, and high incidence of lymphoreticular malignancies. One of the most devastating symptoms of A-T — cerebellar ataxia — develops progressively into general motor dysfunction. Based on our previous studies we hypothesized that the neurological deficits in genomic instability disorders stem (at least in part) from significant reduction in functionality of glial cells. We further hypothesized that impaired vascularization affects the environment in which the neurons and glial cells function, thereby reducing neuronal cell functionality. We found that ATM deficiency led to aberrant astrocytic morphology and alterations of vasculature both in cerebellum and the visual system. Moreover, we found reduced myelin basic protein immunoreactivity and signs of inflammation in ATM-deficient cerebella and optic nerve.  Interestingly, similar findings have been reported in patients with other genomic instability disorders. These observations bolster the notion that astrocyte-specific pathologies and hampered vascularization and astrocyte-neuron interactions in the CNS play crucial roles in the etiology of genome instability brain disorders and underlie brain degeneration at specific sites.


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OMP_2016_04_0028.pdf950.57 KB
Published ahead of print July 04, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 153-163; doi:10.20388/OMP2016.002.0030
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The name astroglia unifies many non-excitable neural cells that act as primary homeostatic cells in the nervous system. Neuronal activity triggers multiple homeostatic responses of astroglia that include increase in metabolic activity and synthesis of neuronal preferred energy substrate lactate, clearance of neurotransmitters and buffering of extracellular K+ ions to name but a few. Many (if not all) of astroglial homeostatic responses are controlled by dynamic changes in the cytoplasmic concentration of two cations, Ca2+ and Na+. Intracellular concentration of these ions is tightly controlled by several transporters and can be rapidly affected by activation of respective fluxes through ionic channels or ion exchangers. Here we provide a comprehensive review of astroglial Ca2+ and Na+ signalling.


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OMP_2016_02_0030.pdf457.26 KB
Published ahead of print July 03, 2016; Printed July 23, 2016; OM&P 2016 Volume 2 Issue 2, pages 164-171; doi:10.20388/OMP2016.002.0031
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Thyroid hormones (THs) are essential for the development and function of the central nervous system (CNS), not only for neuronal cells but also for glial development and differentiation. In adult CNS, both hypo- and hyper-thyroidism may affect psychological condition and potentially increase the risk of cognitive impairment and neurodegeneration including Alzheimer’s disease (AD). We have reported non-genomic effects of tri-iodothyronine (T3) on microglial functions and its signaling in vitro (MORI et al., 2015). Here we report the effects of hyperthyroidism on glial cells in vivo using young and old male and female mice. Immunohistochemical analyses showed glial activation are sex- and age-dependent. We also injected fluorescent-labeled amyloid β peptide (Aβ1-42) intracranially to L-thyroxine (T4)–injected hyperthyroid model mice and observed sex-dependent microglial phagocytosis in vivo as well. These results may partly explain the gender- and age-dependent differences in neurological and psychological symptoms of thyroid dysfunction.


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OMP_2016_02_0031.pdf1.23 MB

Supplement S 2 | June 2016

Published ahead of print June 29, 2016; Printed June 30, 2016; OM&P 2016 Volume 2 Supplement S 2, pages 1-17; doi:10.20388/OMP2016.00S2.001
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CELLULAR NEUROSCIENCE.pdf504.76 KB
Published ahead of print June 29, 2016; Printed June 30, 2016; OM&P 2016 Volume 2 Supplement S 2, pages 18-34; doi:10.20388/OMP2016.00S2.002
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MOLECULAR NEUROSCIENCE.pdf556.75 KB
Published ahead of print June 28, 2016; Printed June 30, 2016; OM&P 2016 Volume 2 Supplement S 2, pages 35-50; doi:10.20388/OMP2016.00S2.003
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Published ahead of print June 28, 2016; Printed June 30, 2016; OM&P 2016 Volume 2 Supplement S 2, pages 51-63; doi:10.20388/OMP2016.00S2.004
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COMPUTATIONAL NEUROSCIENCE.pdf919.89 KB
Published ahead of print June 28, 2016; Printed June 30, 2016; OM&P 2016 Volume 2 Supplement S 2, pages 64-80; doi:10.20388/OMP2016.00S2.005
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Published ahead of print June 28, 2016; Printed June 30, 2016; OM&P 2016 Volume 2 Supplement S 2, pages 81-114; doi:10.20388/OMP2016.00S2.006
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school.pdf1.72 MB
Published ahead of print June 21, 2016; Printed June 30, 2016; OM&P 2016 Volume 2 Supplement S 2
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autors index.pdf116.71 KB

Issue 1 | March 2016

Published ahead of print January 18, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 1-10; doi:10.20388/OMP2016.001.0019
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The common denominator of neurodegenerative diseases, which mainly affect humans, is the progressive death of neural cells resulting in neurological and cognitive deficits. Astroglial cells are central elements of the homoeostasis, defence and regeneration of the central nervous system, and their malfunction or reactivity contribute to the pathophysiology of neurodegenerative diseases. Pathological remodelling of astroglia in neurodegenerative context is multifaceted. Both astroglial atrophy with a loss of function and astroglial reactivity have been identified in virtually all forms of neurodegenerative disorders. Astroglia may represent a novel target for therapeutic strategies aimed at preventing and possibly curing neurodegenerative diseases.


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OMP_2016_01_0019.pdf584.08 KB
Published ahead of print January 17, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 11-26; doi:10.20388/OMP2016.001.0024
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A conspicuous ability of the mammalian brain to integrate and process huge amount of spatial, visual and temporal stimuli is a result of its enormous structural complexity functioning in an integrated way as a whole. Here we review recent achievements in the understanding of brain structure and function. A traditional view on the brain as a network of neurons has been extended to the more complicated structure including overlapping and interacting networks of neurons and glial cells. We discuss artificial versus natural neural networks and consider a concept of attractor networks. Moreover, we speculate that each neuron can have an intracellular network on a genetic level, based and functioning on the principle of artificial intelligence. Hence, we speculate that mammalian brain is, in fact, a network of networks. We review different aspects of this structure and propose that the study of brain can be successful only if we utilize the concepts recently developed in nonlinear dynamics: the concept of integrated information, emergence of collective dynamics and taking account of unexpected behavior and regimes due to nonlinearity. Additionally, we discuss perspectives of medical applications to be developed following this research direction.


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OMP_2016_01_0024.pdf1.8 MB
Published ahead of print January 17, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 27-33; doi:10.20388/OMP2016.001.0022
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Classically, the central nervous system (CNS) was considered to contain neurons and three main types of glial cells - astrocytes, oligodendrocytes, and microglia.  Now, it has been clearly established that NG2-glia are a fourth glial cell type that are defined by their expression of the NG2 chondroitin sulfate proteoglycan (Cspg4).  NG2-glia are also known as oligodendrocyte precursor cells (OPCs) and express the alpha receptor for platelet-derived growth factor (Pdgfra) as well as other oligodendrocyte lineage markers. NG2-glia are most numerous during CNS development when they are responsible for massive generation of oligodendrocytes, the myelin-forming cells of the CNS. A significant population of NG2-glia persist in the adult CNS, where they generate oligodendrocytes throughout life. A unique feature of NG2-glia is that they receive synaptic inputs from neurons and are able to respond rapidly to neurotransmission via their specific ion channel and receptor profiles. Moreover, synaptic and neuronal integrity depend on NG2-glia. Notably, concomitant disruption of NG2-glia, myelin and neurotransmission are key features of many neuropathologies, including Multiple Sclerosis and Alzheimer’s disease (AD). The fact that neurotransmission both regulates and is reliant on NG2-glia and myelin raises the ‘chicken and egg’ question of what comes first – disruption of NG2-glia/myelin or synapses/neurons. It is more useful to think of neurons, NG2-glia and oligodendrocytes/myelin as being functionally integrated and interdependent units, whereby disruption of any one can result in a vicious cycle with potentially devastating effects on CNS function.

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OMP_2016_01_0022.pdf909.28 KB
Published ahead of print January 17, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 34-43; doi:10.20388/OMP2016.001.0017
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Astrocytes are now recognised as important contributors to synaptic transmission control. Dopamine is a key neuromodulator in the mammalian brain and establishing the potential extent of its actions involving astrocytes is vital to our overall understanding of brain function. Astrocyte membranes can express receptors for dopamine, as well as dopamine transporters, but the full effects of dopamine on astrocytic physiology are still uncertain and its mode of action controversial. Here we overview the developing field of astrocyte-dopamine interaction, focusing on how dopamine affects the pre-eminent astrocytic intracellular signalling messenger – Ca2+ – and the available evidence for astrocyte-mediated effects of dopamine on neurons. We then discuss some of the methodological issues that need to be addressed to help move the field forward.


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OMP_2016_01_0017.pdf817.55 KB
Published ahead of print January 17, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 44-54; doi:20388/OMP2016.001.0020
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Most of the human brain mass is occupied by the neocortex, which consists of neurons and non-neurons. The latter cells include astrocytes, a heterogeneous glial cell type. While astrocytes have been considered as neuronsubservient entities for almost a century, it is now becoming evident that they are essential in providing homeostatic support to neural networks and that they also actively participate in information processing in the brain. Astrocytes get excited when neurotransmitters bind to their membrane receptors and feed-back by releasing their own signals. This involves vesicles, which store chemicals termed gliotransmitters or more generally gliosignaling molecules. In the former case chemical messengers get released from astrocytic sites proximal to the synapse, which defines communication to occur in the micro-space of contact between the synapse and the astrocyte. In contrast gliosignaling molecules may also be released into the extracellular space. This mode of release resembles the endocrine system. Hence astrocytes are considered to be part of the gliocrine system in the brain, where the glymphatic system mediates the convection of released molecules. This complex system not only plays a role in cell-to-cell communication but also synchronizes the provision of energy for neural networks. Astrocytes contain glycogen, a form of energy store. Excitation of astrocytes by volume transmitters, such as noradrenaline , released by locus coeruleus neurons, activates adrenergic receptors and stimulates glycogenolysis, providing lactate. This chapter briefly reviews how noradrenaline and astrocytes operate to synchronize excitation and energy provision. Moreover, Ca2+ -dependent fusion of the vesicle membrane with the plasma membrane in astrocytes is discussed.

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OMP_2016_01_0020.pdf1.74 MB
Published ahead of print January 16, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 55-62; doi:20388/OMP2016.001.0023
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Stem cells research has passed a long and exciting way from the discovery to clinical applications. Every year more-and-more scientific reports and solid research breakthroughs are published in this fascinating field making it difficult to follow after new discoveries and cover the history. In the current review we overviewed history of stem cells research starting from the discovery and ending with the current state-of-art. We discussed obstacles and future perspectives of the cell-based therapy, with a special focus made on protection and regeneration of the lost functions after injury/degeneration of adult central nervous system.


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OMP_2016_01_0023.pdf482.95 KB
Published ahead of print January 16, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 63-68; doi:20388/OMP2016.001.0021
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The effect of 2-aminoethyl diphenylborinate (2-APB), a commonly used drug to modulate inositol-1,4,5-triphosphate (IP3) receptors and transient receptor potential (TRP) channels, on GABAA receptor-mediated currents was studied in neurons from the medial preoptic nucleus (MPN) of rat. 2-APB gradually and reversibly reduced the currents evoked by GABA but had no effect on the currents evoked by glycine. The blocking effect was not mediated by alterations in intracellular calcium concentration and showed a concentration dependence with half maximal effect at ~50 µM 2-APB, for currents evoked by 100 µM, as well as by 1.0 mM GABA, suggesting that 2-APB is not competing with GABA for its binding site at the GABAA receptor. Thus, the present study describes a novel pharmacological property of 2-APB as a non-competitive blocker of GABAA receptors and calls for caution in the interpretation of the results where 2-APB is used to affect IP3 receptors or TRP channels.


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OMP_2016_01_0021.pdf995.14 KB
Published ahead of print January 16, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 69-76; doi:20388/OMP2016.001.0025
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Malignant gliomas are primary brain tumors considered to be one of the deadliest cancers. Despite surgical intervention followed by aggressive radio- and chemo-therapies, average survival is approximately 15 months of diagnosis. Recurrent tumors resembling all the characteristics of the original tumor mass and growing in close vicinity to the original site are frequent due to presence of a self-renewing population of cells, glioma stem cells. The cells are resistant to therapies and able to invade the surrounding healthy brain tissue. Indeed, infiltrative growth assisted by numerous interactions with microenvironment are hallmarks of glioma growth. Many research efforts are put forward to understand the mechanisms of invasion. Glioma cells adopted numerous biological strategies to their own advantage to viciously propagate and navigate narrow spaces within the brain. Despite enormous amount of data on malignant gliomas generated by –omics approach which broaden our knowledge on glioma physiology in the last decade, parallel success in discovering new therapies did not happen. Thus, new therapeutic approaches may employ healthy cells of the microenvironment to tame malignant growth are necessary. Here, we highlight current knowledge on glioma origin, infiltrative growth, interactions with the microenvironment and potentials for new therapies.


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OMP_2016_01_0025.pdf427.69 KB
Published ahead of print January 16, 2016; Printed March 04, 2016; OM&P 2016 Volume 2 Issue 1, pages 77-86; doi:10.20388/OMP2016.001.0018
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Alzheimer’s disease (AD) is the most common cause of dementia with an increasing impact on the aging society. Although generations of researchers tried to unravel the pathomechanisms behind this disease, the molecular and cellular mechanisms leading to its onset and progression are still far from being completely understood. Accordingly, only a symptomatic treatment is available until now, and a curative treatment seems to be far-off. On the other hand, several novel therapeutic strategies have been proposed and debated during the last decade. Because of the extensive serotonergic denervation that has been observed in the AD brain and the important role played by serotonin in both, cognition and behavioural control, this neurotransmitter system has become a focus of a concerted research effort to identify new treatments for AD. Therefore, modulation of defined serotonin receptors by specific ligands represents a promising tool for treatments for neurodegenerative diseases like AD. Here we provide an overview of the involvement of the serotonergic system in AD and discuss the underlying molecular mechanisms. 

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Supplement S1 | December 2015

Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 21-22; doi:10.20388/omp2015.00s1.001
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The medial preoptic nucleus is critically involved in the social type of behavior regulation, such as parental behaviour, social recognition, sexual behaviour, ect.. A big amount of studies are focused on the role of glutamate, GABA, serotonin, and dopamine systems of medial preoptic area (mPOA) in the social types of behaviour regulation. However, the role of glycinergic system in this nucleus has not been investigated.


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10.20388omp2015.00s1.001.pdf597.01 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 20-21; doi:10.20388/omp2015.00s1.002
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The aim of the investigation was to assess antihypoxic and neuroprotective properties of the glial cell line-derived neurotrophic factor (GDNF) in hypoxia models in vitro and in vivo. In vitro experiments were carried out on primary hippocampal cultures. Hypoxia modeling was performed on day 14 of culture development in vitro (DIV) by replacing the normoxic cultural medium with a medium containing low oxygen for 10 minutes. Registration of extracellular action potentials was conducted by MEA systems (Multichannel Systems, Germany) application. Study the effect of GDNF on synaptic plasticity was performed using SmartFlare RNA Detection Probes (Merck Millipore, France) and fluorescent microscopy. In vivo experiments were carried out on C57BL/6j male mice. For acute hypobaric hypoxia a vacuum flow-through chamber was used at the ambient temperature of 20–22°C. We have investigated the resistance of animals to hypoxia and their spatial memory retention in Morris water maze test 24 hours after hypoxia. In vitro and in vivo data demonstrated that GDNF has strong antihypoxic and neuroprotective properties. Preventive GDNF application before hypoxia contributed to the animal survival and spatial memory retention as well as the maintenance of cells viability in primary hippocampal cultures. 


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10.20388omp2015.00s1.002.pdf761.93 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 19; doi:10.20388/omp2015.00s1.003
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To identified genetic cause of congenital hypoplasia cerebellum in two families with different syndromes high- throughput sequencing analysis was performed. X-linked non-progressive ataxia in first family from Mongolian ancestry was caused by genetic defects in ABCB7 gene and modifying by ATP7A gene.


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10.20388omp2015.00s1.003.pdf296.59 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 18; doi:10.20388/omp2015.00s1.004
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Today many fundamental questions in Neuroscience can be addressed with Microfluidics methods which provide unique approaches for cell patterning and control neural branch outgrowth. Such methods can be used to gwoe separate subpopulations of dissociated neurons connected with uni-directional connectivity. Combined with microelectrode arrays such approach can be used to simulate and study neurogenesis, learning and information coding in neural networks.


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10.20388omp2015.00s1.004.pdf245.71 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 16-18; doi:10.20388/omp2015.00s1.005
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In this study we developed microfluidic structure with two neuronal cultures grown in separated chambers and connected by microchannels for axon outgrowth. We estimated bursting activity transfer characteristics between chambers in relation toculture development and determine rate of axonal growth in chambers.


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10.20388omp2015.00s1.005.pdf542.87 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 15-16; doi:10.20388/omp2015.00s1.006
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The aim of the investigation was to study a role of cannabinoid receptors type 1 (СВ1) and type 2 (СВ2) in implementation of antihypoxic and neuroprotective effects of N-ADA in hypoxia model in vitro. The experiments were carried out on primary hippocampal cultures. N-ADA effect on the spontaneous bioelectrical and calcium network activity in dissociated hippocampal cultures in normal and hypoxic conditions as well as the role of CB1 and CB2 in the implementation of these effects were investigated. Registration of extracellular action potentials was conducted by MEA systems (Multichannel Systems, Germany) application. For the detection of patterns of spontaneous calcium oscillations we used fluorescent calcium dye Oregon Green 488 BAPTA-1 AM (Invitrogen) and a confocal laser scanning microscope (Zeiss LSM510, Germany). Study the expression of mRNA CB1 receptors was performed using SmartFlare RNA Detection Probes (Merck Millipore, France) and fluorescent microscopy. Our data demonstrated that N-ADA has strong antihypoxic and neuroprotective properties associated with activation of cannabinoid receptors type 1. 


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10.20388omp2015.00s1.006.pdf474.34 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 14-15; doi:10.20388/omp2015.00s1.007
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10.20388omp2015.00s1.007.pdf499.92 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 12-14; doi:10.20388/omp2015.00s1.008
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In this work we report two successful cases of developing neural networks of spiking neurons for controlling mobile robots. In the first case we use a toy robot, a crocodile, driven by a neural network in-silico. We show that this so-called neuroanimat is capable of detecting internal events of synchronization of network responses to stimuli. In the second example we employ a spiking neural network for building a human-robot interface. Using a bracelet with eight electromyographic sensors we have shown that the interface can faithfully detect myographic signals, classify them according to hand gestures, and send the corresponding commands to the robot. Although the two applications belong to different areas of Neuroscience, they are based on a common approach of neural computations. We note that in both cases besides neural networks there are no additional external algorithms for the decision-making. 


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10.20388omp2015.00s1.008.pdf563.34 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 10-11; doi:10.20388/omp2015.00s1.009
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The study was designed to investigate the effect of verapamil on the speed of propagation of electrical excitation in the myocardium. As a result, it was found that verapamil reduces heart rate, the speed of excitation in the myocardium remains unchanged. The results obtained allow us to estimate the effect of verapamil on the condition of cardiac tissue, based on the change in its conductivity during treatment with the drug.


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10.20388omp2015.00s1.009.pdf247.44 KB
Published ahead of print December 01, 2015; Printed December 01, 2015; OM&P 2015 Volume 1 Supplement S1, pages 10; doi:10.20388/omp2015.00s1.0010
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