Issue 1 | March 2021
Photodynamic therapy (PDT) is a promising approach in the treatment of various tumors. The presence of three essential components: a photosensitizer, a light source and oxygen is required for generating reactive oxygen species and subsequent tumor destruction. In this study, we investigated the cell death pathway induced by Photodithazine (PD) mediated photodynamic therapy (PD-PDT). We found that PD localizes in the endoplasmic reticulum and Golgi apparatus of cancer cells. Upon irradiation at 20 J/cm2, PD induced death of tumor cells at concentrations exceeding 100 nM. Based on dying cell morphology, exposure of phosphatidylserine to the cell surface, presence of phosphorylated form of mixed lineage kinase domain like pseudokinase (pMLKL) and protective action of pan-caspase inhibitor and inhibitor of receptor-interacting protein kinase 1 (RIPK1), we hypothesize that Photodithazine forces cells to enter mixed-type cell death with features of apoptosis and necroptosis.
|7 Mechanisms of photodynamic killing of cancer cells by photodithazine.pdf||1.13 MB|
We have explored the features of PPARγ2 gene alleles expression in elderly patients with comorbid conditions such as obesity and coronary artery disease. 140 patients of both sexes (54.3% men and 45.7% women) aged 60-89 were examined. The main group included 70 pts with CHD; the control group included 70 pts without CHD. Pro12 allele carrier state in the main group was 85%, and Ala12 allele carrier state – 15%. Pro12Ala and Ala12Ala genotypes, Ala12 allele were detected more often in patients with coronary artery disease than in the control group (p = 0.0008 and p = 0.0003, respectively). Pro12Ala genotypes (OR = 2.02, CI = 1.28–3.19, p = 0.003) and Ala12Ala (OR = 2.002, CI = 1.32–3.04, p = 0.0006) of Ala12 gene PPARγ2 carrier state increases the risk of CHD developing by 2 times. It was confirmed that nuclear PPARs are capable of controlling development, differentiation, metabolic homeostasis and reproduction. The role of various genotypes of the PPARγ2 gene in the regulation of lipid metabolism and angiogenesis in comorbid conditions in elderly patients may help to identify new methods of their treatment.
Currently, radionuclide therapy of tumors using sources of alpha and beta radiation is actively developing. However, the radiosensitivity of tumor cells has been studied mainly using acute gamma radiation. In this regard, studies aimed at determining the ranges of radiosensitivity of cells of various origins in relation to beta-emission radionuclides are gaining relevance. The study was carried out on A431, CHO and SK-BR-3 cell lines using beta-emission sealed sources Sr-90+Y-90. Cell viability was assessed via MTT-assay. Dose dependences were obtained for irradiating cells with a beta source: the LD50 range was from 17 to 19 Gy, and LD37 was from 24 to 36 Gy. It was shown that at the same dose of radiation, the percentage of viable cells relative to the control of 72 hours after irradiation is significantly less than after 24 hours. The revealed LD50 values for tumor cells under chronic beta-irradiation are higher than with acute gamma-irradiation, which should be considered when selecting doses during the development of potential radiopharmaceutical treatment. Decreased cell viability in response to beta radiation is due to both cytotoxic and cytostatic manifestations.
CuO in the form of micro- and nano-sized colloidal particles enters the human body from environment. The aim of the study is the identification of morphological changes in rat liver tissues during chronic oral intake of micro- and nanosized CuO by image analysis. The experiments were performed on 45 male Wistar rats (3 groups: experimental (nanosized CuO); comparison (micro-sized CuO); control (water without CuO)). Suspensions CuO were administered to the rats orally once a day. Quantitative morphological parameters were determined by pathomorphological examination and image analysis using the method of constructing Voronoi diagrams (the ratio of cells of various shapes); average cell area; the average size of the cell perimeter and the number of cells per unit area. As a result of the analysis by the constructing Voronoi diagrams, was found that the main part of the model cells corresponding to hepatocytes has the shape of a hexagon. In the control group, their share is 35.89%, in the experience group – 29.09%, and in the comparison group – 30.59%. The density of cells’ distribution in the comparison group is 7 times higher than in the control group; in the experimental group the same indicator is 4 times higher than in the control group. Collectively, the characteristics of morphological changes in liver tissue indicate greater toxicity of nano-sized copper oxide compared to its micro-sized analogue.
The world’s biggest killer is ischemic heart disease, responsible for 16% of the world’s total deaths. Since 2000, the largest increase in deaths has been for this disease, rising by more than 2 million to 8.9 million deaths in 2019. In recent years, many studies have shown that hydrogen has therapeutic and preventive effects in various human and animal disease models. In this study, we investigated the possible antioxidant effects of molecular hydrogen in erythrocytes and blood plasma in rats with the experimentally simulated chronic heart failure. We estimated the intensity of lipid peroxidation processes by the contents of diene and triene conjugates, Schiff bases, malonic dialdehyde, catalase activity. The results from this study suggest that inhalation of 2% molecular hydrogen leads to a decrease in pro-oxidant and an increase in antioxidant parameters. The results of this study provide the basic data for the mechanism research and application of molecular hydrogen in the future.
Achieving both deep penetration of photons into biological tissue and highly sensitive recording of optical probes' response are the key goals of non-invasive optical imaging. In comparison with the traditional fluorescence imaging in the visible (400–700 nm) and near-infrared (700–900 nm) regions, optical fluorescence imaging in the second optical tissue transparency window (1000–2300 nm) demonstrates low photon scattering, deeper penetration into the tissues and lower autofluorescence. In the present study, biocompatible upconversion nanoparticles with different contents of doping lanthanides, capable of luminescence in the visible and short-wave IR regions, were obtained and characterized. Also, targeted complexes based on Gd-containing nanophosphors were obtained as potential contrast agents for magnetic resonance imaging. Selective binding of targeted complexes to the surface of tumor cells expressing the HER2 receptor was shown.
Epilepsy affects around 1% of the population in the world. Thus, it is imperative that new more effective and safe treatments be found. In order to understand the nature of epilepsy, new and better animal models are needed in that they offer valuable resources for researchers. Such models provide an opportunity to characterize seizures in the whole organism, to understand the molecular basis of these processes and to test the effectiveness of treatments and therapies. In this study, we have shown that screening after chemical mutagenesis can be used as a tool to identify new genes that may be involved in the mechanism of epilepsy formation.
|1 ENU mutagenesis as a tool for identifying novel mouse models of epilepsy.pdf||663.99 KB|
Issue 4 | December 2020
Over the past two decades, developments in the field of nanobiomedicine have come a long way despite the unresolved hindrances. The creation and development of effective theranostic agents based on nanomaterials are urgent needs of modern medicine. Upconversion nanoparticles (UCNP) appear to be the most promising agents for developing theranostics due to their unique optical properties. There has been extensive research on new approaches to obtain stable colloids capable of prolonged circulation in the bloodstream, particularly with bovine serum albumin (BSA). The present work contributes to solving the problem of obtaining stable agents based on UCNP by coating water-soluble UCNPNOBF4 with a stable protein corona layer of BSA. The assembled nanocomplex is promising for usage as a diagnostic agent and is set for further investigation.
|The Assembly оf а Photoluminescent Nanocomplex Based оn Upconversion Nanoparticles.pdf||487.42 KB|
Methylation of DNA cytosine bases is a key epigenetic modification that plays an important role in the regulation of gene expression and the formation of the epigenome. Numerous studies of the human genome show that there is a close relationship between DNA methylation, age and sex of a person. Until now, the popular model has been the linear change in the methylation level with age. Here we find a fundamentally different DNA methylation behavior, namely the nonlinear dependence of the methylation level on age. We identify CpG probes whose methylation changes exponentially with age or according to a power law, and perform Gene Ontology enrichment analysis of the latter. Our results are relevant to understanding how DNA methylation changes with age and the found nonlinear CpG sites can be used to construct new epigenetic clocks.
|DNA Methylation in Aging- Beyond the Linear Processes.pdf||729 KB|
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.
|Morphological Disturbances of Brain Structures in Traumatic Brain Injury.pdf||1.05 MB|
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.
|Heart and Mind Interaction for ADHD.pdf||642.68 KB|
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.
|Genetic Variants of H.pylori in Different Forms of Chronic Gastritis.pdf||474.77 KB|
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.
|Features of Karyotype Changes in Centenarians.pdf||398.86 KB|
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.
|The Particularities of Organism Stress Reaction Development under the Influence of Bee Venom.pdf||610.34 KB|
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.
|Research of Erythrocytes Membranes Change by Laser Interference Microscopy.pdf||691.41 KB|
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.
|Extraction of Functional State Patterns Based on Amplitude-Phase Coupling of ECG.pdf||415.85 KB|
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.
|FUNCTIONAL CONJUGATION OF RBC ELECTROPHORETIC MOBILITY.pdf||483.42 KB|
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.
|CONTRIBUTION OF NOVOSIBIRSK RESEARCH SCHOOLS.pdf||263.28 KB|
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.
|CYTOGENETIC EFFECTS OF COMPLEX POLLUTION.pdf||313.34 KB|
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.
|CULTIVATION OF PRIMARY HIPPOCAMPAL CELL CULTURES.pdf||804.93 KB|
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.
|Features of Lipid Metabolism of the Indigenous Inhabitants.pdf||326.67 KB|
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.
|Evolutionary Expansion of the Neocortex.pdf||602.18 KB|
Supplement S 1 | May 2019
|Function and plasticity of synapses.pdf||475.73 KB|
|Cortical circuits in health and disease.pdf||461.69 KB|
|Neuron-glia interactions.pdf||500.76 KB|
|author index.pdf||284.76 KB|
|Development of cortical neuronal networks.pdf||968.59 KB|
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.
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.
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.
|A Methodology of Calcium Dynamics Registration in Presynaptic Terminals of Neurons In Situ.pdf||411.64 KB|
|Evolving Brains with New Genes.pdf||2.06 MB|
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.
|Mechanisms and Neuronal Control of Vocalization in Vertebrates.pdf||6.86 MB|
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
|Cognitive neuroscience.pdf||404.8 KB|
|Neuromorphic and neurohybrid systems.pdf||12.93 MB|
|System biology and age-related diseases.pdf||15.55 MB|
|Neurodynamics and artificial intelligence.pdf||18.67 MB|
|Molecular and cellular neuroscience 1.1.pdf||15.74 MB|
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.
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.
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.
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.