Issue 4 | December 2020
3D bioengineering constructs are currently a promising area of research in the regeneration of various tissues. In our work, several modifications of scaffolds based on hyaluronic acid glycidyl methacrylate are presented. Scaffolds have been tested for biocompatibility with nerve cells in an in vivo model of traumatic brain injury. Throughout the experiment, the neurological status of the animals was monitored, and at the end, a histological examination of the brain was carried out. It has been shown that scaffolds are non-toxic to nerve cells and reduce the development of neurological deficit in animals in the post-traumatic period. The possibility of using the scaffold with a lower biodegradation rate as a carrier of a therapeutic drug has also been demonstrated.
Decellularized matrices of animal organs can serve as a promising platform for creating highly relevant threedimensional in vitro models of tumor growth. In this work, the applicability of two decellularization protocols for obtaining the extracellular matrices of various murine organs was examined. The resulting decellularized matrices were characterized by visual integrity and preservation of the tissue architectonics. A high degree of the cellular component elimination was demonstrated while maintaining the basic structures of the extracellular matrix. From the point of view of convenience and ease of use, as well as the quality of the obtained matrices, the method based on the use of detergent sodium dodecyl sulfate and trypsin-aprotinin complex has demonstrated the greatest suitability. In the future, the developed protocol will be used to study tumor-matrix interaction and tissue-specific characteristics of growth and morphology of tumor cells.
An experimental trauma was performed for the studying of morphological changes characteristics of the brain under the action of neuroprotectors soon after the brain injury. The closed craniocerebral injury was modeled by the free fall of a load on the parietooccipital area of the brain. We made repeat studies of the influence of succinate medicaments (cytoflavin and mexicor) on histological examination and morphometric analysis of the microcirculatory bed of the cerebral cortex. The experiments were made on the 1st, 3rd, 7th, and 12th day after the traumatic brain injury. An experimental morphological study has established that the use of neuroprotetors after the trauma recovers of brain tissue and positively affects the angio- and cytoarchitectonics of the cerebral cortex in the posttraumatic period.
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Issue 3 | September 2020
ADHD is considered one of the most common neurobehavioral disorders of childhood and among the most prevalent chronic health conditions affecting school-age children. This makes research of psychophysiological correlates of ADHD very important. The aim of our pilot study was to find out the specific aspects of autonomic regulation of a sensorimotor activity in children with ADHD. To assess objectively the functional state dynamics of the children, the technology of event-related telemetry of the heart rate was used (cogni-nn.ru, Lobachevsky State University). This technology integrates the ApWay.ru Web platform for the controlled activation of primary cognitive functions. The conducted study allowed us to reveal some specific aspects of sensorimotor activity and autonomic regulation for children with ADHD. A digital map of psychophysiological status based on the integration of indicators of sensorimotor activity and event-related parameters of autonomic regulation can be an effective tool to increase the specificity, sensitivity and reliability of the diagnosis of ADHD in children.
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The development of clinical forms of infection and endoscopic changes in the gastric mucosa depends on the H.pylori genetic diversity in a given region. The aim of this work was to study the relationship of the genetic profile of H.pylori pathogenicity factors with clinical and endoscopic features of Helicobacter-associated gastritis in Nizhny Novgorod. A number of H.pylori pathogenicity genes of DNA isolates obtained by endoscopy from 151 patients with chronic H.pylori-associated gastritis (non-destructive, erosive, and atrophic) were studied by PCR. Results. In destructive processes in the gastric mucosa, the detection frequency of cagA, vacA s1 m1 genes and a combination of several pathogenicity factors, including iceA A1 and babA was higher than in other forms of gastritis. Atrophic gastritis is characterized by the genetic profile cagA and vacA s2 m2. Infection with several H.pylori strains is determined more often in erosive gastritis and atrophy of the gastric mucosa. Conclusions. In chronic gastritis in Nizhny Novgorod, a predominantly "European" character of the pathogen population structure was revealed - with a moderate content of the most pathogenic cagA, vacA s1-positive strains. Colonization of the gastric mucosa by H.pylori with a genetic structure containing pathogenicity factors cagA, vacA, babA, ice A2, in chronic H.pylori-associated diseases, it is a factor in increasing the severity, activity and prevalence of the inflammatory process, the appearance of signs of atrophy of the gastric mucosa. The greatest influence on these indicators is exerted by the presence of cagA and vacA s1 in the microorganism genome, as well as a combination of several pathogenicity factors.
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Genomic instability is one of the biomarkers of aging. Studies show that the spontaneous level of chromosomal aberrations in lymphocytes increases with age. However, it is not yet fully understood whether there is an agedependent increase in genomic instability. The aim of this study was to establish the patterns of the influence of age on the level of chromosomal aberrations in human lymphocytes. For this purpose, the spontaneous frequency of chromosomal aberrations, mitotic activity and the number of aneuploidies in the lymphocytes of centenarians (people over 85 years old) were assessed. A standard cytogenetic research method was used. It was shown that the overall frequency of chromosomal aberrations in peripheral blood lymphocytes in centenarians was significantly higher than in the control group. It was revealed that there is a decrease in the mitotic activity of lymphocytes in the sample of centenarians, while the level of aneuploidies corresponds to the control group. It was also found that, despite the fact that the total number of aberrations increases with age, a decrease in the frequency of deletions is observed in the group of centenarians. No correlation was found between biological age and the frequency of aberrations.
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The research of stress reaction under the influence of bee venom and immobilization on rat is made in this paper. It is demonstrated that the stress reaction is developed under the influence of both factors. However, it’s shown that the second phase of stress reaction connected with hypothalamo-pituitary-adrenal axis activation and glucocorticoid concentration increase predominates in case of bee venom injection. The revealed prolongation of the second, compensatory phase may define the organism resistance increase after the bee venom injection and bee venom therapeutic action.
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Issue 2 | July 2020
The possibility of using laser interference microscopy to explore the morphological and functional state of erythrocytes was studied. The possibilities of this method based on the rapid determination of the structure and physiological state of erythrocytes were shown. The analysis of erythrocytes by laser interference microscopy showed that erythrocytes have a typical biconcave discocyte shape. On erythrocytes’ surface, there is a slight heterogeneity due to the presence of membrane-bound proteins. The impact on erythrocytes of stress hormones caused changes in erythrocyte surface that were different from physiologically normal. Numerous loosening of the structure appeared on cell surface during erythrocyte incubation with cortisol. Incubation of cells with adrenaline caused a greater effect of erythrocyte membranes deformation which was expressed by the appearance of convex seals and spicules on the surface. The molecular mechanisms of membrane modifications arising under the action of adrenaline and cortisol were discussed. The results of the work may be interesting both for basic research of erythrocyte properties and for practical medicine.
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The features of ischemic brain injury outcome in C57BL/6 mice depending on the right or left common carotid artery occlusion are characterized. The right-hemispheric focal ischemia decreases the body weight, causes spatial memory impairment, and activates the development of a pronounced long-term neurological deficit characterized by ipsilateral limb paralysis, ptosis and muscle dystrophy, which is accompanied by perivascular brain tissue edema. In the left-hemispheric focal ischemia, the neurological status impairments are also observed, but they less pronounced than in case of right-hemispheric ischemia. Moreover, preference to study novelty is reduced, and long-term emotional strain is revealed. The peculiarity of ischemic injury using the left common carotid artery occlusion is accompanied by the presence of hemorrhages and dilated capillaries in the damaged brain hemisphere.
The present study is dedicated to the investigation of slow-waves in heart rate activity of healthy persons. Approaches to the description of the cardiovascular functional states using the dynamic characteristics of the amplitudephase coupling mechanisms of the electrocardiographic signal are described. Amplitude-phase coupling based pattern extracting was carried out. Suggested informative features and patterns of regulatory systems will allow the analysis of the diagnostic procedure results with reference to the central mechanisms of regulation and control.
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The aim of this study was to examine the antidepressant-like responses to vitamin D3 (VD3) subcutaneous (s.c.) supplementation (1.0, 2.5, and 5.0 mg/kg) in middle-aged long-term ovariectomized (OVX) rats treated with a low dose of 17β-estradiol (17β-E2) (0.5 μg/rat, s.c.) exposed to the chronic unpredictable mild stress (CUMS). Sucrose preference (SPT), forced swimming (FST), and open-field (OFT) tests were performed to measure anhedonia, depressionlike state, and locomotor/grooming activities, respectively. Glial cell line-derived factor (GDNF) levels in the hippocampus of middle-aged long-term OVX rats following CUMS treated with VD3 were measured using ELISA and Western blotting. The serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the hippocampus were detected by high performance liquid chromatography (HPLC). The findings demonstrated that VD3 (1.0 mg/kg, s.c.) in a combination with a low dose of 17β-E2 increased sucrose consumption in the SPT and decreased depression-like behavior in the FST of middle-aged long-term OVX rats exposed to CUMS. This dose of VD3 elevated hippocampal GDNF protein expression and increased 5-HT/5-HIAA levels in middle-aged long-term OVX rats plus 17β-E2 compared to the middle-aged OVX rats plus 17β-E2 with CUMS. The other two doses of VD3 (2.5 and 5.0 mg/kg, s.c.) failed to modify both GDNF protein levels and 5-HT turnover in the hippocampus of middle-aged long-term OVX rats treated with 17β-E2 exposed to CUMS. Thus, treatment with a low dose of VD3 (1.0 mg/kg, s.c.) in a combination with a low dose of 17β-E2 enhanced antianhedonic-/antidepressant-like effects of both substances in middle-aged long-term OVX rats exposed to CUMS.
Issue 1 | March 2020
In this paper we studied the RBC electrophoretic mobility, cytomorphological and cytogenetic parameters of buccal epithelial cells and morphology of adrenal glands under the influence of adrenalin which was injected to simulate a stress in rat body. It’s established that an initial increase of the activity of brain substance neuroendocrinocytes (during the first hour) with further increase of the activity of the adrenal cortex (from 1 day) are combined with the change of RBC electrophoretic mobility index: at first it decreases and then it increases. Besides the cells with signs of cytotoxic changes appear. The absence of cells with karyopyknosis in stressed animal bodies indicates that the mechanisms of natural resistance of buccal epithelial cells preserve. It’s associated with the development of adaptive processes.
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The article presents a brief history of the formation of scientific ideas about kidney physiology and the mechanisms of water-salt metabolism regulation in Novosibirsk, as well as the role of some physiologists in the development of these views. The beginning of the development of renal physiology in Novosibirsk was the idea by A.G. Ginetsinsky about the reflex osmoregulatory system of the organism, that was developed by his students (L.K. Velikanova, Ya.D. Finkinstein, L.N. Ivanova, Yu.V. Natochin, L.I. Kurduban). Later on, the veiws about the ion-regulating mechanisms and age-specific features of their formation in the ontogenesis of humans and animals have been formed (A.Ya. Terner, R.I. Aizman, I.V. Pantyukhin). The role of interconnections in this direction between the researchers from Novosibirsk and scientists from the USA (L. Rabinowitz), Sweden (A. Aperia, G. Celsi), Israel (H. Garty, S. Karlish) and others were shown. Knowledge of the history of the development of renal physiology in different countries and the results of cooperation between researchers play an important role in understanding the development prospects of this scientific area.
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The assessment of micronucleus species in erythrocyte of amphibians living in different hydrochemical conditions of water bodies of the Nizhni Novgorod region in the dynamics of four-year monitoring (2016-2019) was carried out. The content of erythrocyte of blood of Pelophylax ridibundus decreased, the proportion of erythrocyte with micronuclei increased, the ratio of different types of micronuclei changed, attached micronucleidue prevailed in erythrocytes. In the blood of Pelophylax ridibundus, attached micronuclei were found 2.1 times more often than in P. lessonae.
A positive relationship was established between the sum of all types of micronuclei (ρ = 0.61), the number of erythrocytes with attached micronuclei (ρ = 0.64) and the content of sulfates in the water; the number of erythrocytes with loosened micronuclei and the content of nitrites (ρ = 0.47). Negative associations were found between: the content of erythrocytes in the blood and the complex pollution of the water (ρ = -0.47) and the concentration of manganese (ρ = -0.54); the proportion of erythrocytes with rod-shaped micronuclei and a general level of pollution (ρ = -0.54), as well as with the content of manganese in the water (ρ = -0.50). The results obtained reflect the ecological dysfunction of the habitat and indicate significant violations of the cytogenetic homeostasis of the organism of amphibians in the urbanized territory.
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Correlation microscopy is an invaluable tool for studying the functional and structural features of individual cells. Here we present an approach for the cultivation of primary hippocampal cultures grown on a special substrate that allows drawing a convenient coordinate grid. The metabolic activity and immunocytochemical labeling of neurons were estimated, as well as the patch-clamp method and ultrastructural analysis.
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Issue 3, 4 | December 2019
Diseases of the circulatory system and neoplasms are among the leading causes of death worldwide. Mountain Altai is characterized by low life expectancy and unfavorable climate in the highlands, which affects the nutritional characteristics of the indigenous population. The aim of the study was to assess the parameters of lipid metabolism in connection with the nutrition of the indigenous population of Mountain Altai. The quantitative composition of macronutrients of the daily diet and biochemical parameters of blood plasma of the high altitude population were estimated. Suffcient consumption of animal protein by the aborigines of the Mountain Altai and high consumption of saturated fatty acids and monounsaturated fatty aсids were revealed, which depends on the mountain bioclimatic, which allows to engage exclusively in cattle breeding. In men, between the consumption of monounsaturated fatty acids and the concentration of cholesterol in the blood plasma an inverse correlation was revealed, indicating the activity of the system that provides effective utilization of plasma cholesterol and maintenance of lipid homeostasis. Despite the stability of the blood plasma lipid parameters in the examined group, there is a risk of lipid homeostasis violation in the case of maladaptation processes and under stress conditions, which requires monitoring of these parameters in the dynamics.
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Issue 2 | September 2019
The neocortex is a major part of the mammalian brain and a key structure for human behavior, cognition and language. During the course of brain evolution, the neocortex in many mammalian species underwent an increase in its size and complexity, which is thought to provide a basis for the increased cognitive abilities of humans. The differences in neocortex size and complexity between various mammalian species stem from developmental processes that regulate the production of neocortical neurons. Neural stem and progenitor cells with their unique cell biological characteristic are instrumental for such developmental processes. In this review we will discuss key aspects of the evolutionary expansion of the neocortex, and specifically the features present during fetal/embryonic development. We will then discuss the cell biological characteristics of neural stem and progenitor cells and mechanisms underlying the evolutionary expansion of the neocortex.
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Supplement S 1 | May 2019
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Issue 1 | March 2019
Computational models for two neuron/astrocyte networks are developed to explore mechanisms underlying the astrocytes’ role in maintaining neuronal firing patterns. For the first network, a single neuron receives periodic excitatory inputs at varying frequencies. We consider the role played by several astrocytic dendritic processes, including the Na+-K+ ATPase pump, K+ channels and gap junctions in maintaining extracellular ion homeostasis so that the neuron can faithfully sustain spiking in response to the excitatory input. The second network includes two neurons coupled through mutual inhibitory synapses. Here we consider the role of astrocytic dendritic processes in maintaining anti-phase or synchronous oscillations. Dynamical systems methods, including bifurcation theory and fast/slow analysis, is used to systematically reduce the complex model to a simpler set of equations. In particular, the first network, consisting of differential equations for the neuron and astrocyte membrane potentials, channel state variables and intracellular and extracellular Na+ and K+ concentrations, is reduced to a one dimensional map. Fixed points of the map determine whether the astrocyte can maintain extracellular K+ homeostasis so the neuron can respond to periodic input.
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Axo-axonal interactions of neuronal cells play an important role in functional development during embryogenesis. Axons of the cells formed on early stages of the brain development provide a template for the growing axons of later axons. However, the mechanisms of the guiding of younger axons by already formed axons are not well understood. In this study, we present a method to study such axo-axonal interactions in vitro using microfluidics methods and culturing neocortical cells. We studied the dynamics of axon growth in microchannels perpendicularly intersecting with other microchannels. This study provides fundamental understanding of the axonal navigation in microfluidic structures, which further facilitate the design of experimental in vitro model for studying the role of already formed axons in the development of neuronal system.
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Issue 3, 4 | December 2018
In this study we examined the intersection of two molecular pathways both known to regulate dentate development – the Emx2 transcription factor and the Sonic Hedgehog (Shh) morphogenic scignaling pathway. We confirmed that Emx2 mutant mice have a markedly reduced dentate gyrus and studied evidence of changes in Shh signaling and Shh expression in these mutants. Our results indicate that loss of Emx2 affects the numbers and distribution of Gli+ ventrally derived dentate neural stem cells that are responsible for populating the perinatal dentate gyrus. Accompanying this, we find that Emx2 mutants have reduced expression of Shh in the amygdalo-hippocampal region. In addition, there are ectopic Shh responsive progenitors that fail to properly populate the dentate. Taken together our results indicate that Emx2 regulates dentate development in part by altering availability and signaling of Shh.
For many decades synaptic circuits have been associated solely with cell-cell neuronal connections represented by the presynaptic terminal, which releases a neurotransmitter, and the postsynaptic neuronal specialization, a site where the neurotransmitter can activate synaptic receptors. However, due to technical limitations these studies usually were linked only to the postsynaptic site. For a long while, the widespread techniques that rapidly advanced neurophysiology have been little used in understanding the way how Ca2+-dependent release of the excitatory neurotransmitter glutamate from neuronal axons can be measured directly. Only with the advance of live cell imaging, it became possible to detect internal Ca2+ dynamics in presynaptic boutons with the high temporal resolution.
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Issue 2 | September 2018
Parkinson's disease is a progressive age-associated neurological disorder. One of the major neuropathological hallmarks of Parkinson’s disease is the appearance of protein aggregates, mainly consisting of the protein alpha-Synuclein. These aggregates have been described both in genetic as well as idiopathic forms of the disease. Currently, Parkinson’s disease patient-specific induced pluripotent stem cells (iPSCs) are mainly used for in vitro disease modeling or for experimental cell replacement approaches. Here, we demonstrate that these cells can be used for in vivo disease modeling. We show that Parkinson’s disease patient-specific, iPSC-derived neurons carrying the LRRK2-G2019S mutation show an upregulation of alpha-Synuclein after transplantation in the mouse brain. However, further investigations indicate that the increased human alpha-Synuclein levels fail to induce spreading or aggregation in the mouse brain. We therefore conclude that grafting of these cells into the mouse brain is suitable for cell autonomous in vivo disease modeling but has strong limitations beyond that. Furthermore, our results support the hypothesis that there might be a species barrier between human to mouse concerning alpha-Synuclein spreading.
The convoluted human cerebral cortex is one of the key features that allows for an increased neuronal density packing essential for the complex cognitive and socioemotional behaviours man possesses. Nevertheless, the underlying mechanisms involved in cortical folding remained a both intriguing and functionally important enigma. A crucial component known to be involved in the formation and maintenance of all tissues is the extracellular matrix (ECM), providing scaffolds which tie tissues and organs in place. The composition of the ECM in both developing and mature structures is constantly remodelled, degraded and secreted by numerous types of cells, and its role as a source of growth factors and signalling in morphogenesis, migration, and proliferation is increasingly appreciated. Evidence for the differential expression of ECM during gyrification pinpoints its potentially fundamental role in shaping the folds of the cerebral cortex through both mechanical and molecular configurations. This review aims at addressing key ideas, potential directions and discoveries that highlight biomechanics of the ECM during the construction of the cortex cerebral gyrification.
Vocalization is a highly conserved innate behavior in vertebrates. It is mainly used in social encounters to communicate a variety of information for inter- and intra- specific interactions. In this review, we focus on the anatomical, biomechanics and neuronal circuits underlying vocalization across vertebrate species. In addition, we discuss our recent findings that assign to the nucleus of the solitary tract a critical role in innate vocalization. This brain center receives viscerosensory information, i.e. information from internal organs that includes the lungs and the larynx. Furthermore, subpopulations of neurons in the nucleus of the solitary tract directly connect to and entrain the activity of expiratory and laryngeal motor neurons. In mammals and amphibians, these motor neurons control essential biomechanical parameters used for vocalization, and similar motor neuron pools regulate vocal utterances in birds. Thus vocalization relies on a conserved neuronal circuit residing in the brainstem and spinal cord.
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The present study was performed to determine the behavioral effects of cholecalciferol (Vitamin D3) hormone treatment at different doses as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol on depression-like behavior of female rats after long-term absence of estrogen. The aim of the study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, SC once daily, for 14 days) on depression-like behavior following long-term ovariectomy (12 weeks) of the adult (3 months old) female rats of Wistar line. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with low dose of 17β-estradiol (17β-E2, 0.5 μg/rat, SC once daily, for 14 days) after long-term ovariectomy. Depression-like behavior was assessed in the forced swimming test (FST), locomotor and grooming activities were assessed in the open field test (OFT). Using biochemical studies were evaluated estradiol and 25-hydroxyvitamin D3 levels in the blood serum of OVX rats treated with cholecalciferol alone and cholecalciferol plus 17β-E2. Chronic administration of cholecalciferol (5.0 mg/kg/day, SC) into the intact females significantly reduced depression-like behavior in the FST (p<0.05). The treatment with cholecalciferol (1.0 mg/kg/day, SC) in the OVX rats after long-term absence of estrogens induced antidepressant-like effect (p<0.05) in the FST. Moreover, cholecalciferol in this dose plus 17β-E2 more markedly exhibited antidepressant-like effect in the OVX rats after longterm ovariectomy (p<0.05). Simultaneously, treatment with cholecalciferol (1.0 mg/kg/day, SC) in the OVX rats after longterm absence of estrogens produced elevated estradiol and 25-OH-VD3 levels for the OVX rats as compared to the OVX females. The combined application of cholecalciferol (2.5 and 5.0 mg/kg/day, SC) and 17β-E2 produced antidepressantlike effect that was similar to the antidepressant-like effect of 17β-E2. Our results indicate that cholecalciferol at dose of 5.0 mg/kg/day induced antidepressant-like effect only in intact rats subjected FST. Following long-term ovariectomy in the adult female rats, cholecalciferol at dose of 1.0 mg/kg/day administered alone resulted in decrease of depression-like behavior in the FST. Moreover, cholecalciferol at dose of 1.0 mg/kg/day in a combination with 17β-E2 at a low dose induced synergic antidepressant-like effect in the FST.
Supplement S 1 | June 2018
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Issue 1 | March 2018
Ionic homeostasis in the brain involves redistribution of ionic fluxes in several cell types and compartments, including neurons, astrocytes and the extracellular space. How the major ionic activity-dependent fluxes of potassium and sodium are individually regulated remains difficult to dissociate and to track experimentally. We here review recent progress in modeling the ionic fluxes evoked by neuronal activity based on mass conservation. Excitability of neurons indeed relies on inward sodium and outward potassium fluxes during action potential firing. Recently, we have developed a tri-compartment model based on mass-action kinetics equations that account for potassium dynamics between neurons, astrocytes and the extracellular space. This review describes how such type of model can be used to spatially and temporally predict potassium fluxes during various regimes of neuronal activity. In particular, the model initially showed that it takes several seconds for astrocytes to buffer the majority of the potassium rapidly released by neurons in both basal and high regime of activity. Such model can also probe the selective contribution of ionic channels, and revealed for instance that disruption of the main astroglial potassium Kir4.1 channels not only favors the emergence of epileptiform activity, but also dysregulates neuronal excitability specifically during slow rhythmic activities. We here also extend the predictions of the model by assessing the selective contribution of the astroglial and neuronal Na/K ATPase, or volume of the extracellular space on potassium dynamics. We discuss these findings and their implications for neuronal information processing in the healthy and diseased brain.
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The goal of the work was to study the effect of the cannabinoid receptor agonist WIN55,212-2 and the cannabinoid type 1 receptor antagonist AM251 on electrophysiological changes in the hippocampus and the medial septal region (MS) induced by the intracerebral administration of excitotoxin kainic acid. Kainate injected into the right brain ventricle provoked persistent seizures (status epilepticus, SE) in all rats. A morphological analysis of the right hippocampus performed one month after the SE revealed the death of neurons, which was most pronounced in the hilus of the dentate gyrus and in the CA3a field of the dorsal hippocampus. In brain slices taken one month after the SE, the spontaneous activity of MS neurons and population EPSP (pEPSP) in the CA1 field of the hippocampus evoked by the stimulation of Shaffer collaterals (SC) was recorded; the changes in the activity were compared with the activity in slices of healthy animals injected with normal saline (“control slices”). It was found that the activity in MS slices from the brain of animals injected with kainic acid (“kainate slices”) was almost twice higher than in the control. After the application of WIN55,212-2, the frequency of discharges in the control did not change, whereas in kainate slices, the level of neuronal activity decreased to the control value. The application of AM251 led to an increase in the frequency of discharges in the control and its decrease in kainate slices. The registration of pEPSPs in the hippocampal slices revealed a twofold increase in the responses to SC stimulation in kainate slices compared with those in the control, i.e., an abrupt increase in neuronal excitability. A tendency for a decrease in excitability after the application of WIN55,212-2 and, conversely, for its increase by the action of AM251 was noted in evoked responses in the hippocampal kainate slices. Our results allow to assume the protective impact of cannabinoid agonist WIN55,212-2 on neuronal activity in the medial septum and hippocampus that disturbed by neurotoxic kainate influence.
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Сlassical bioindicators – amphibians – were used to assess the quality of the environment and detect cytogenetic disorders. There are immature erythrocytes with rounded micronuclei in the bone marrow cells. The merging and transformation of micronuclei occurs in the process of mitotic division and erythrocytes maturing. It leads to a prepotency in the bloodstream of erythrocytes with disintegrated micronuclei and an attached micronucleus. An integrated research study of the environment using the cytogenetic characteristics of living organisms is called for.
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Issue 3, 4 | December 2017
Synchrony in neuronal networks plays a crucial role in the functioning of the brain. Stability of synchrony is most desirable to prevent any emergent desynchrony due to natural events, internal or external disturbances. The brain might have its own mechanism to repair its desynchrony, otherwise, some external procedure might be necessary to restore synchrony. We propose here a mechanism to realize robust synchrony in neuronal networks against parameter drifting. A selective addition of cross-coupling links over and above the conventional diffusive coupling links is found [Saha et al. (2017)] recently that makes dramatic improvements in the stability of synchrony of dynamical networks and that saves synchrony against breakdown due to parameter drifting. We apply the concept to realize globally stable synchrony in neuronal networks and the desired effect of robust synchrony and, present our numerical studies with examples of network motifs and a larger network of neurons and using the Hindmarsh-Rose (HR) [Hindmarsh and Rose (1984)] slow-fast neuron model for each node of the networks.
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This review focuses on temperature dependence of biophysical properties of ion channels of other than TRP types. Some functional consequences of the channels temperature sensitivity for neuronal excitation in health and disease are considered.
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Neurons of the substantia nigra are most prone to degeneration in Parkinson’s disease. The cause of their vulnerability remains unclear and knowledge of the molecular and microstructural features of the substantia nigra pars compacta will help understanding why nigral neurons are vulnerable to damaging factors.
The present study was aimed to investigate the intranuclear inclusions of the nigral neurons, the Marinesco bodies and the Roncoroni rodlets, which origin and function are uncertain, using ubiquitin-, tyrosine hydroxylase-, nitric oxide synthase-, calbindin-, NeuN-, glutamic acid decarboxylase-, and α-tubulin-immunohistochemistry and iron histochemistry with DAB enhancement.
Of the tested substances, tyrosine hydroxylase and nitric oxide synthase were revealed for the first time in the Marinesco bodies. Non-heme iron was found for the first time in both the Marinesco bodies and the Roncoroni rodlets. In accordance with previous studies, ubiquitin-immunoreactivity was demonstrated in the Marinesco bodies. Moreover, we describe some smaller round and dot-like ubiquitin-immunoreactive structures in the nucleus of melanized neurons. The found small ubiquitin-immunopositive structures within the nucleus are proposed to be the developmental stages of growing Marinesco bodies, whereas Marinesco bodies themselves seem to label the neurons with impaired function of proteasome.
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Recurrent epileptiform activity induces network sodium oscillations in the juvenile hippocampus. In CA1 pyramidal neurons, these oscillations are mainly caused by opening of glutamate-gated ion channels, while in astrocytes, sodium increases are due to sodium-dependent glutamate uptake. Astrocytes express the glutamate transporters GLAST and GLT- 1, which exhibit differential expression patterns during postnatal development. The specific contribution of these transporter subtypes to sodium oscillations is not known. We addressed this question by performing somatic sodium imaging in hippocampal tissue slices from neonatal (postnatal days (P) 2-4) and two-week-old (P14-16) mice. We found that perfusion with Mg2+-free, bicuculline-containing saline caused sodium oscillations in both developmental stages. Moreover, at both P2-4 and P14-16, application of TFB-TBOA to inhibit GLAST and GLT-1 generated fast sodium loading of neurons and termination of oscillatory activity, accompanied by loss of membrane integrity of neurons, while astrocytes experienced only minor increases in baseline sodium. DHK, a GLT-1-specific blocker, induced moderate sodium loading of neurons, reduced the amplitude of neuronal sodium oscillations and increased the oscillation frequency in two-week-old mice. In neonatal animals, DHK increased baseline sodium and reduced the peak amplitude of sodium transients as well, but exerted only moderate effects on network activity. Taken together, our experiments demonstrate the essential role of glutamate uptake for sodium homeostasis and neural function already in the early neonatal brain. Moreover, they suggest that, although GLAST dominates in neonatal tissue and GLT-1 is predominant at P14-16, both transporter subtypes functionally contribute to glutamate clearance during the first three weeks after birth.
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The aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c., once daily, for 14 days) on the anxiety-like and depression-like behaviors following long-term ovariectomy (12 weeks) in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol after long-term absence of estrogen (17β-E2, 0.5 µg/rat, s.c., once daily, for 14 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM), depression-like behavior was assessed in the forced swimming test (FST), locomotor and grooming activities were assessed in the open field test (OFT). The treatment with cholecalciferol (1.0 mg/kg/day, s.c.) in the OVX rats after long-term absence of estrogens induced antidepressant-like effect (p<0.05). Moreover, cholecalciferol in this dose plus 17β-E2 more markedly exhibited antidepressant-like effect in the OVX rats after long-term ovariectomy (p<0.05). The OVX rats treated with cholecalciferol at doses of 1.0 mg/kg and 2.5 mg/kg demonstrated a decrease of anxiety-like behavior in the EPM. The combination of cholecalciferol at doses of 1.0 and 2.5 mg/kg with a low dose of 17β-E2 more effectively decreases anxiety-like behavior in the OVX rats after long-term estrogen deficiency than17β-E2 alone. This work promotes more effective creation of novel therapeutic targets and strategies for affective-related disorders treatment in female subjects with long-term estrogen deficiency.
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Supplement S 1 | September 2017
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Issue 2 | June 2017
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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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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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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