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Blood-brain barrier (BBB) is a structural and functional element of the neurovascular unit (NVU), which includes cells of neuronal, glial, and endothelial nature. The main functions of NVU include maintenance of the control of metabolism and chemical homeostasis in the brain tissue, ensuring adequate blood flow in active regions, regulation of neuroplasticity processes, which is realized through intercellular interactions under normal conditions, under stress, in neurodegeneration, neuroinfection, and neurodevelopmental diseases. Current versions of the BBB and NVU models, static and dynamic, have significantly expanded research capabilities, but a number of issues remain unresolved, in particular, personification of the models for a patient. In addition, application of both static and dynamic models has an important problem associated with the difficulty in reproducing pathophysiological mechanisms responsible for the damage of the structural and functional integrity of the barrier in the diseases of the central nervous system. More knowledge on the cellular and molecular mechanisms of BBB and NVU damage in pathology is required to solve this problem. This review discusses current state of the cellular and molecular mechanisms that control BBB permeability, pathobiochemical mechanisms and manifestations of BBB breakdown in stress and neurodegenerative diseases, as well as the problems and prospects of creating in vitro BBB and NVU models for translational studies in neurology and neuropharmacology. Deciphering BBB (patho)physiology will open up new opportunities for further development in the related areas of medicine such as regenerative medicine, neuropharmacology, and neurorehabilitation.

Alzheimer’s – disease is a progressive neurodegenerative disorder in which the accumulation of β‑amyloid and neurofibrillary tangles is a determining pathological sign. Activation of RAGE plays a decisive role in the production and aggregation of β-amyloid, formation of neurofibrillary tangles and degeneration of neurons. The aim of this work is to assess the influence of RAGE and its ligands—β-amyloid (Aβ1-42) on endothelial cells of cerebral microvascular in model blood-brain barrier (BBB) in vitro with experimental Alzheimer’s disease. Modeling of experimental Alzheimer’s disease in vitro caused a significant (P ≤ 0.05) increase expression of RAGE on endothelial cells and decrease in the transendothelial electric resistance (TEER) in both the static and dynamic models BBB. However, suppressed expression of RAGE led to a persistent and long-term increase value of TEER. In this case, the ligand RAGE-Ab1-42 caused reduced parameters of TEER. Alzheimer’s disease is accompanied by pathological changes in the expression of RAGE on endothelial cells, thereby leading to altered structural and functional integrity of the BBB. Blocking the RAGE expression in cerebral endothelial cells inhibits development of endothelial dysfunction and restores integrity of BBB impaired by the action of β-amyloid.

A common feature of neurodegenerative disorders, in particular Alzheimer's disease (AD), is a chronic neuroinflammation associated with aberrant neuroplasticity. Development of neuroinflammation affects efficacy of stem and progenitor cells proliferation, differentiation, migration, and integration of newborn cells into neural circuitry. However, precise mechanisms of neurogenesis alterations in neuroinflammation are not clear yet. It is well established that expression of NLRP3 inflammasomes in glial cells marks neuroinflammatory events, but less is known about contribution of NLRP3 to deregulation of neurogenesis within neurogenic niches and whether neural stem cells (NSCs), neural progenitor cells (NPCs) or immature neuroblasts may express inflammasomes in (patho)physiological conditions. Thus, we studied alterations of neurogenesis in rats with the AD model (intra-hippocampal injection of Aβ1-42). We found that in Aβ-affected brain, number of CD133+ cells was elevated after spatial training in the Morris water maze. The number of PSA-NCAM+ neuroblasts diminished by Aβ injection was completely restored by subsequent spatial learning. Spatial training leads to elevated expression of NLRP3 inflammasomes in the SGZ (subgranular zones): CD133+ and PSA-NCAM+ cells started to express NLRP3 in sham-operated, but not AD rats. Taken together, our data suggest that expression of NLRP3 inflammasomes in CD133+ and PSA-NCAM+ cells may contribute to stimulation of adult neurogenesis in physiological conditions, whereas Alzheimer's type neurodegeneration abolishes stimuli-induced overexpression of NLRP3 within the SGZ neurogenic niche.

Early life stress (ELS) is one of the most critical factors that could modify brain plasticity, memory and learning abilities, behavioral reactions, and emotional response in adulthood leading to development of different mental disorders. Prenatal and early postnatal periods appear to be the most sensitive periods of brain development in mammals, thereby action of various factors at these stages of brain development might result in neurodegeneration, memory impairment, and mood disorders at later periods of life. Deciphering the processes underlying aberrant neurogenesis, synaptogenesis, and cerebral angiogenesis as well as deeper understanding the effects of ELS on brain development will provide novel approaches to prevent or to cure psychiatric and neurological deficits caused by stressful conditions at the earliest stages of ontogenesis. Neuropeptide oxytocin serves as an amnesic, anti-stress, pro-angiogenic, and neurogenesis-controlling molecule contributing to dramatic changes in brain plasticity in ELS. In the current review, we summarize recent data on molecular mechanisms of ELS-driven changes in brain plasticity with the particular focus on oxytocin-mediated effects on neurogenesis and angiogenesis, memory establishment, and forgetting.

New RAGE- and CD147-mediated mechanisms of damage to the hippocampus of mice due to the accumulation of amyloid β (Aβ), the development of local inflammation, metabolic disorders and damage to the blood–brain barrier in two experimental models of Alzheimer’s disease were studied in vivo. The new effects of Aβ in the hippocampal tissue in chronic Alzheimer’s type neurodegeneration, which characterize neuroplasticity disorders, were studied, as were angiogenesis, the structural and functional integrity of the blood–brain barrier, and the development of local neuroinflammation in conjunction with the features of the expression of RAGE and CD147 proteins. Early neurodegenerative changes in the hippocampus associated with the accumulation of Aβ are associated with the intensification of neoangiogenesis and the formation of aberrant intercellular contacts in the endothelial layer of cerebral microvessels in individual hippocampal subregions and the development of local neuroinflammation. As neurodegeneration progresses, neoangiogenesis in the hippocampus is suppressed.

Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. In recent years, attention of researchers has increasingly been focused on studying the role of brain insulin resistance (BIR) in the AD pathogenesis. Neuroinflammation makes a significant contribution to the BIR due to the activation of NLRP3 inflammasome. This study was devoted to the understanding of the potential therapeutic roles of the NLRP3 inflammasome in neurodegeneration occurring concomitant with BIR and its contribution to the progression of emotional disorders. Methods: To test the impact of innate immune signaling on the changes induced by Aβ1-42 injection, we analyzed animals carrying a genetic deletion of the Nlrp3 gene. Thus, we studied the role of NLRP3 inflammasomes in health and neurodegeneration in maintaining brain insulin signaling using behavioral, electrophysiological approaches, immunohistochemistry, ELISA and real-time PCR. Results: We revealed that NLRP3 inflammasomes are required for insulin-dependent glucose transport in the brain and memory consolidation. Conclusions NLRP3 knockout protects mice against the development of BIR: Taken together, our data reveal the protective role of Nlrp3 deletion in the regulation of fear memory and the development of Aβ-induced insulin resistance, providing a novel target for the clinical treatment of this disorder.

The excitation/inhibition (E/I) balance controls the synaptic inputs to prevent the inappropriate responses of neurons to input strength, and is required to restore the initial pattern of network activity. Various neurotransmitters affect synaptic plasticity within neural networks via the modulation of neuronal E/I balance in the developing and adult brain. Less is known about the role of E/I balance in the control of the development of the neural stem and progenitor cells in the course of neurogenesis and gliogenesis. Recent findings suggest that neural stem and progenitor cells appear to be the target for the action of GABA within the neurogenic or oligovascular niches. The same might be true for the role of neuropeptides (i.e. oxytocin) in neurogenic niches. This review covers current understanding of the role of E/I balance in the regulation of neuroplasticity associated with social behavior in normal brain, and in neurodevelopmental and neurodegenerative diseases. Further studies are required to decipher the GABA-mediated regulation of postnatal neurogenesis and synaptic integration of newly-born neurons as a potential target for the treatment of brain diseases.

Early life stress (ELS) causes long-lasting changes in brain plasticity induced by the exposure to stress factors acting prenatally or in the early postnatal ontogenesis due to hyperactivation of hypothalamic-pituitary-adrenal axis and sympathetic nervous system, development of neuroinflammation, aberrant neurogenesis and angiogenesis, and significant alterations in brain metabolism that lead to neurological deficits and higher susceptibility to development of brain disorders later in the life. As a key component of complex pathogenesis, ELS-mediated changes in brain metabolism associate with development of mitochondrial dysfunction, loss of appropriate mitochondria quality control and mitochondrial dynamics, deregulation of metabolic reprogramming. These mechanisms are particularly critical for maintaining the pool and development of brain cells within neurogenic and angiogenic niches. In this review, we focus on brain mitochondria and energy metabolism related to tightly coupled neurogenic and angiogenic events in healthy and ELS-affected brain, and new opportunities to develop efficient therapeutic strategies aimed to restore brain metabolism and reduce ELS-induced impairments of brain plasticity.

Ectoenzyme and receptor BST-1/CD157 has been considered as a key molecule involved in the regulation of functional activity of cells in various tissues and organs. It is commonly accepted that CD157 catalyzes NAD+ hydrolysis and acts as a component of integrin adhesion receptor complex. Such properties are important for the regulatory role of CD157 in neuronal and glial cells: in addition to recently discovered role in the regulation of emotions, motor functions, and social behavior, CD157 might serve as an important component of innate immune reactions in the central nervous system. Activation of innate immune system in the brain occurs in response to infectious agents as well as in brain injury and neurodegeneration. As an example, in microglial cells, association of CD157 with CD11b/CD18 complex drives reactive gliosis and neuroinflammation evident in brain ischemia, chronic neurodegeneration, and aging. There are various non-substrate ligands of CD157 belonging to the family of extracellular matrix proteins (fibronectin, collagen I, finbrinogen, and laminin) whose activity is required for controlling cell adhesion and migration. Therefore, CD157 could control structural and functional integrity of the blood-brain barrier and barriergenesis. On the other hand, contribution of CD157 to the regulation of brain development is rather possible since in the embryonic brain, CD157 expression is very high, whereas in the adult brain, CD157 is expressed on neural stem cells and, presumably, is involved in the neurogenesis. Besides, CD157 could mediate astrocytes’ action on neural stem and progenitor cells within neurogenic niches. In this review we will summarize how CD157 may affect brain plasticity acting as a molecule at the crossroad of neurogenesis, cerebral angiogenesis, and immune regulation.

Neuroinflammation has been classified as a trigger of behavioral alterations and cognitive impairments in many neurological conditions, including Alzheimer's disease, major depression, anxiety and others. Regardless of the cause of neuroinflammation, key molecules, which sense neuropathological conditions, are intracellular multiprotein signaling inflammasomes. Increasing evidence shows that the inflammatory response, mediated by activated nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasomes, is associated with the onset and progression of a wide range of diseases of the CNS. However, whether the NLRP3 inflammasome in the CNS is involved in the learning, development of anxiety and adult neurogenesis remains elusive. Therefore, the present study was designed to assess NLRP3 inflammasome contribution in anxiety and reveal its potential involvement in the experimental acquisition of fear responses and hippocampal neurogenesis. Behavioral, immunohistochemical and electrophysiological alterations were measured to evaluate role of neuroinflammation in the limbic system of mice. In this study, we describe interrelated neurophysiological mechanisms, which culminate in absence of NLRP3 inflammasome in young 4 months mice. These include the following: anxious behavior and deterioration in learning and memory of fear conditioning; impairment of adult neurogenesis; reduction and altered morphology of astrocytes in the brain; hyperexcitability in basolateral amygdala (BLA); impaired activation in axons of pyramidal cells of CA1 hippocampal zone in NLRP3 KO mice particularly via the Schaffer collateral pathway; and impaired synaptic transduction in pyramidal cells mediated by an embarrassment of neurotransmitter release from presynaptic site in CA3 hippocampal zone. The present study has demonstrated the novel findings that basal level of NLRP3 inflammasome in the brain of young mice is required for conditioning-induced plasticity in the ventral hippocampus and the basolateral amygdala. The deletion of NLRP3 impair synaptic transduction and caused anxiety-like behavior and labored fear learning, suggesting that low grade inflammation, mediated by NLRP3 expression, play a key role in memory consolidation.

Social recognition is the sensitive domains of complex behavior critical for identification, interpretation and storage of socially meaningful information. Social recognition develops throughout childhood and adolescent, and is affected in a wide variety of psychiatric disorders. Recently, new data appeared on the molecular mechanisms of these processes, particularly, the excitatory-inhibitory (E/I) ratio which is modified during development, and then E/I balance is established in the adult brain. While E/I imbalance has been proposed as a mechanism for schizophrenia, it also seems to be the common mechanism in autism spectrum disorder (ASD). In addition, there is a strong suggestion that the oxytocinergic system is related to GABA-mediated E/I control in the context of brain socialization. In this review, we attempt to summarize the underpinning molecular mechanisms of E/I balance and its imbalance, and related biomarkers in the brain in healthiness and pathology. In addition, because there are increasing interest on oxytocin in the social neuroscience field, we will pay intensive attention to the role of oxytocin in maintaining E/I balance from the viewpoint of its effects on improving social impairment in psychiatric diseases, especially in ASD.

Introduction: Alzheimer’s disease is a chronic neurodegenerative disease leading to neuropsychiatric disorders and cognitive decline. A number of studies demonstrate an important role of the mitogen-activated protein kinase (MAPK) pathway and NLRP3 inflamasomes in β-amyloid metabolism impairment and insulin resistance in Alzheimer’s disease. Objective: To study the expression of NLRP3 in the cells of neuronal and glial nature, as well as the expression of MAPK in the amygdala neurons in animals with experimental Alzheimer’s disease. Materials and methods: Subjects of the study: (1) CD1 mice (males, 4 months old) divided in 2 groups, the experimental group (intra-hippocampal exposure to β-amyloid) and the control group (sham-operated animals); (2) mice with a genetic model of Alzheimer’s disease, the B6SLJ-line Tg (APPSwFlLon, PSEN1*M146L*L286V) 6799Vas (males, 12 months old) and the corresponding control group, C57BL/6xSJL mice (males, 12 months old). Immunohistochemistry on free-floating sections was applied for the study of NLRP3 and MAPK expression in the brain amygdala. Results: We revealed the statistically significant increase in the number of NeuN/NLRP3-positive cells (p = 0.043) of the amygdala in animals with a genetic model of Alzheimer’s disease (29.05 ± 2.67) compared with the control group of animals (17.10 ± 1.95). A same trend was obvious in β-amyloid-induced neurodegeneration (p = 0.021). Intra-hippocampal exposure to β-amyloid caused the decrease of MAPK expression in the amygdala neurons (5.97 ± 0.66) compared with the sham-operated animals (13.25 ± 2.65) (p = 0.018). This was also seen in animals with a genetic model of the Alzheimer’s disease (p = 0.031). Conclusions: The increase of NLRP3 inflammasomes expression in animals with experimental Alzheimer’s disease was found in neurons, but not in astrocytes, along with a decrease of the MAPK expression in neurons of the amygdala. These findings indicate coupling of the inflammatory process and the disorganization on the insulin-signaling mechanisms of the brain during neurodegeneration.

This literature review demonstrates the importance and consequences of early life stress for the development of the brain and its role in the formation of neurological and mental illnesses (particularly depression). The most dangerous is chronic early life stress during the neonatal period of development in the first days after birth, when the effects on the development of the brain, neuro-, synapto-, and glio-, and angiogenesis are the most stable. Among all the neuropsychological effects of early life stress, the most common are apparent as depressive disorders in humans and animals, and this constitutes a widely used model of experimental depression in rodents.

Alzheimer's disease is characterized by the loss of neurons, the accumulation of intracellular neurofibrillary tangles and extracellular amyloid plaques in the brain. However, there are contradicting data on differences in neurogenesis at the onset of the disease or before the formation of amyloid plaques. As awareness of the importance of the pre-symptom phase in neurodegenerative diseases grows in the context of early diagnosis and pathogenesis, we analyzed the critical periods of adult hippocampal neurogenesis at an early stage under the action of soluble Ab1-42 beta-amyloid. The proliferation, migration and neuronal cells survival were evaluated in mice with an injection of soluble amyloid beta-oligomers. It was found that the injection of Ab1-42 oligomers causes a decrease in cell proliferation in the mouse hippocampus. Despite the preservation of the neuroblast pool in animals after beta-amyloid injection, the process of radial migration is disrupted, and an increase in apoptosis in the neurogenic niche was revealed. Thus, our results demonstrate damage of neurogenesis critical stages: the progenitor cells, neuroblast migration, the integration of immature neurons, and the survival of neurons under application of soluble beta-amyloid oligomers. The obtained data indicate decline in proliferation rate in the subgranular zone, that is accompanied by ectopic differentiation and disturbed migration, producing, apparently, abnormal neurons that have lower survival rates. That could lead to a decrease in mature neurons numbers and the number of cells in the granular layer of the dentate gyrus.Bolezn' Al'tsgeĭmera kharakterizuetsia potereĭ neĭronov, nakopleniem vnutrikletochnykh neĭrofibrilliarnykh klubkov i vnekletochnykh amiloidnykh bliashek v golovnom mozge. Vmeste s tem ostaiutsia protivorechivymi dannye o razlichiiakh v neĭrogeneze v nachale zabolevaniia ili do nachala obrazovaniia amiloidnykh bliashek. Poskol'ku rastet osoznanie vazhnosti predsimptomnoĭ fazy pri neĭrodegenerativnykh zabolevaniiakh v kontekste ranneĭ diagnostiki i patogeneza, nami byli proanalizirovali kriticheskie periody vzroslogo gippokampal'nogo neĭrogeneza na ranneĭ stadii pri deĭstvii rastvorimykh form Ab1-42. V éksperimente s ispol'zovaniem in"ektsionnoĭ modeli bolezni Al'tsgeĭmera na myshakh s vvedeniem rastvorimykh oligomerov Ab byli otseneny proliferatsiia, migratsiia i vyzhivaemost' kletok neĭronal'noĭ prirody. Ustanovleno, chto in"ektsiia rastvorimykh oligomerov Ab vyzyvaet snizhenie proliferatsii kletok v gippokampe mysheĭ. Nesmotria na sokhranenie pula neĭroblastov u zhivotnykh, poluchavshikh Ab narushen protsess radial'noĭ migratsii, a takzhe otmechaetsia uvelichenie apoptoza v neĭrogennoĭ nishe. Takim obrazom, rezul'taty dannogo issledovaniia ukazyvaiut na to, chto vvedenie Ab vyzyvaet narushenie kriticheskikh stadiĭ neĭrogeneza: progenitornoĭ, neĭroblastnoĭ stadii migratsii, stadii integratsii nezrelykh neĭronov i vyzhivaemosti neĭronov. Poluchennye rezul'taty ukazyvaiut na snizhenie skorosti proliferatsii v subgranuliarnoĭ zone, kotoroe soprovozhdaetsia éktopicheskoĭ differentsirovkoĭ i narushennoĭ migratsieĭ, produtsiruia, po-vidimomu, anomal'nye neĭrony, kotorye imeiut bolee nizkie urovni vyzhivaemosti, chto v konechnom itoge mozhet privodit' k umen'sheniiu zrelykh neĭronov i chisla kletok v granuliarnom sloe zubchatoĭ izviliny.

The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aged experimental animals with physiological neurodegeneration. Male outbred CD1 mice used for the study were divided into two groups: group 1 consisted of 12-month-old male mice (physiological aging) and group 2 consisted of 2-month-old male mice (control group). A social recognition 5-trial test, elevated plus maze test (EPM), open field test, light-dark box test, and fear conditioning were used for estimation of the neurological state of experimental animals. We found that aged male mice exhibited lower interest in female mice in the social 5-trial task as compared to young male mice. Increased anxiety was observed in the group of aging mice in the EPM and light-dark box tests as compared to the control group. Lower locomotor activity and increased anxiety were found in the aging rats studied in the open field test. Physiological neurodegeneration was related to impaired associative learning and memory in the group of aging mice, which were observed in fear conditioning; particularly, consolidation of fear memory was dramatically suppressed. Analysis of behavioral factors, social interactions, and anxiety confirmed a model of agerelated neurodegeneration in the aged mice. We suggest that studies on animal behavior in the open field test, light-dark box test, and fear conditioning is the most informative approach for detection of neurological impairments, including deficits of social contacts and interaction, limitation of interests, and increased anxiety, in aging mice. This allows us to get new basic data on behavioral alterations in a model of age-related neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.

Virtual reality (VR) and augmented reality (AR) have become valuable tools to study brains and behaviors resulting in development of new methods of diagnostics and treatment. Neurodegenerаtion is one of the best examples demonstrating efficacy of VR/АR technologies in modern neurology. Development of novel VR systems for rodents and combination of VR tools with up-to-date imaging techniques (i.e. MRI, imaging of neural networks etc.), brain electrophysiology (EEG, patch-clamp), precise analytics (microdialysis) allowed implementing of VR protocols into the animal neurobiology to study brain plasticity, sensorimotor integration, spatial navigation, memory, and decision-making. VR/AR for rodents is а young field of experimental neuroscience and has already provided more consistent testing conditions, less human-animal interaction, opportunities to use a wider variety of experimental parameters. Here we discuss present and future perspectives of using VR/AR to assess brain plasticity, neurogenesis and complex behavior in rodent and human study, and their advantages for translational neuroscience.

Pathophysiology of chronic neurodegeneration is mainly based on complex mechanisms related to aberrant signal transduction, excitation/inhibition imbalance, excitotoxicity, synaptic dysfunction, oxidative stress, proteotoxicity and protein misfolding, local insulin resistance and metabolic dysfunction, excessive cell death, development of glia-supported neuroinflammation, and failure of neurogenesis. These mechanisms tightly associate with dramatic alterations in the structure and activity of the neurovascular unit (NVU) and the blood–brain barrier (BBB). NVU is an ensemble of brain cells (brain microvessel endothelial cells (BMECs), astrocytes, pericytes, neurons, and microglia) serving for the adjustment of cell-to-cell interactions, metabolic coupling, local microcirculation, and neuronal excitability to the actual needs of the brain. The part of the NVU known as a BBB controls selective access of endogenous and exogenous molecules to the brain tissue and efflux of metabolites to the blood, thereby providing maintenance of brain chemical homeostasis critical for efficient signal transduction and brain plasticity. In Alzheimer’s disease, mitochondria are the target organelles for amyloid-induced neurodegeneration and alterations in NVU metabolic coupling or BBB breakdown. In this review we discuss understandings on mitochondria-driven NVU and BBB dysfunction, and how it might be studied in current and prospective NVU/BBB in vitro models for finding new approaches for the efficient pharmacotherapy of Alzheimer’s disease.

An important mechanism of neuronal plasticity is neurogenesis, which occurs during the embryonic period, forming the brain and its structure, and in the postnatal period, providing repair processes and participating in the mechanisms of memory consolidation. Adult neurogenesis in mammals, including humans, is limited in two specific brain areas, the lateral walls of the lateral ventricles (subventricular zone) and the granular layer of the dentate gyrus of the hippocampus (subgranular zone). Neural stem cells (NSC), self-renewing, multipotent progenitor cells, are formed in these zones. Neural stem cells are capable of differentiating into the basic cell types of the nervous system. In addition, NSC may have neurogenic features and non-specific non-neurogenic functions aimed at maintaining the homeostasis of the brain. The microenvironment formed in neurogenic niches has importance maintaining populations of NSC and regulating differentiation into neural or glial cells via cell-to-cell interactions and microenvironmental signals. The vascular microenvironment in neurogenic niches are integrated by signaling molecules secreted from endothelial cells in the blood vessels of the brain or by direct contact with these cells. Accumulation of astrocytes in neurogenic niches if also of importance and leads to activation of neurogenesis. Dysregulation of neurogenesis contributes to the formation of neurological deficits observed in neurodegenerative diseases. Targeting regulation of neurogenesis could be the basis of new protocols of neuroregeneration.

Patch clamp is a golden standard for studying (patho)physiological processes affecting membranes of excitable cells. This method is rather labor-intensive and requires well-trained professionals and long-lasting experimental procedures; therefore, accurate designing of the experiments with patch clamp methodology as well as collecting and analyzing the data obtained are essential for the widely spread implementation of this method into the routine research practice. Recently, the method became very prospective not only for the characterization of single excitable cells but also for the detailed assessment of intercellular communication, i.e. within the neurovascular unit. Here, we analyze the main advantages and disadvantages of patch clamp method, with special focus on the tendencies in clamping technique improvement with the help of patch electrodes for the assessment of intercellular communication in the brain.

Pericytes in the central nervous system attract growing attention of neurobiologists because of obvious opportunities to use them as target cells in numerous brain diseases. Functional activity of pericytes includes control of integrity of the endothelial cell layer, regeneration of vascular cells, and regulation of microcirculation. Pericytes are well integrated in the so-called neurovascular unit (NVU) serving as a platform for effective communications of neurons, astrocytes, endothelial cells, and pericytes. Contribution of pericytes to the establishment and maintaining the structural and functional integrity of blood–brain barrier is confirmed in numerous experimental and clinical studies. The review covers current understandings on the role of pericytes in molecular pathogenesis of NVU/BBB dysfunction in Alzheimer’s disease with the special focus on the development of cerebral amyloid angiopathy, deregulation of cerebral angiogenesis, and progression of BBB breakdown seen in Alzheimer’s type neurodegeneration.

Face recognition is an important index in the formation of social cognition and neurodevelopment in humans. Changes in face perception and memory are connected with altered sociability, which is a symptom of numerous brain conditions including autism spectrum disorder (ASD). Various brain regions and neuropeptides are implicated in face processing. The neuropeptide oxytocin (OT) plays an important role in various social behaviors, including face and emotion recognition. Nasal OT administration is a promising new therapy that can address social cognition deficits in individuals with ASD. New instrumental neurotechnologies enable the assessment of brain region activation during specific social tasks and therapies, and can characterize the involvement of genes and peptides in impaired neurodevelopment. The present review sought to discuss some of the mechanisms of the face distinguishing process, the ability of OT to modulate social cognition, as well as new perspectives and technologies for research and rehabilitation of face recognition.

Aims. Alzheimer’s disease is a multifactorial neurodegenerative disease characterized by the presence of amyloid beta peptide containing plaques, and neurofibrillary tangles. Beta-amyloid is a major risk factor and it plays a central role in the onset and progression of Alzheimer’s disease. However, question of the influence of beta-amyloid on neurogenesis in the hippocampus in the adult brain is still open. The purpose of this paper is to study cognitive functions and their association with proliferation, survival and migration of newly-formed cells in normal adult rat brain and in the experimental Alzheimer’s disease. Materials and methods. Rats (Wistar, males, 7 months) were used. Experimental group (Alzheimer’s disease model with the intrahippocampal administration of beta-amyloid 1-42 (5 µl) bilaterally in the CA1 area) and a control group (sham-operated animals with the intrahippocampal administration of Phosphate buffered salin (5 µl) bilaterally in the CA1) have been tested. The study was conducted from February to July. Neurobehavioral test (Morris water maze) was used to assess working memory and memory consolidation. The study of cell migration was performed by introducing bromodeoxyuridine (50 mg/kg). Expression of neurogenesis markers in the subgranular zone of the dentate gyrus of the hippocampus was studied has been studied with indirect immunohistochemistry for free-floating sections followed by the confocal microscopy. Results. Modelling of Alzheimer’s disease leads to impaired cognitive function and memory in animals. We found that these events were associated with the suppression of proliferative (р = 0,043) and migratory activity of brain cells (р = 0,031), but not survival of cells (p = 0,985) compared to the control group.Training in Morris water maze of animals with experimental Alzheimer’s disease promotes migration of progenitor cells along the rostral migration way (р = 0,011) compared with the group without training. However, the number of neuroblasts (р = 0,809) and proliferation of neuronal progenitor cells (p = 0,083) were not significantly affected compared with the group without training. Conclusions. Decreased level of brain cells proliferation, alterations in their migration and development of cognitive dysfunction have been found in the rat model of Alzheimer’s disease, thus suggesting impairment of neurogenesis induced by amyloid. Possible involvement of local insulin resistance into the development of neurogenesis alterations is discussed.

The blood-brain barrier (BBB) consists of differentiated cells integrating in one ensemble to control transport processes between the central nervous system (CNS) and peripheral blood. Molecular organization of BBB affects the extracellular content and cell metabolism in the CNS. Developmental aspects of BBB attract much attention in recent years, and barriergenesis is currently recognized as a very important and complex mechanism of CNS development and maturation. Metabolic control of angiogenesis/barriergenesis may be provided by glucose utilization within the neurovascular unit (NVU). The role of glycolysis in the brain has been reconsidered recently, and it is recognized now not only as a process active in hypoxic conditions, but also as a mechanism affecting signal transduction, synaptic activity, and brain development. There is growing evidence that glycolysis-derived metabolites, particularly, lactate, affect barriergenesis and functioning of BBB. In the brain, lactate produced in astrocytes or endothelial cells can be transported to the extracellular space via monocarboxylate transporters (MCTs), and may act on the adjoining cells via specific lactate receptors. Astrocytes are one of the major sources of lactate production in the brain and significantly contribute to the regulation of BBB development and functioning. Active glycolysis in astrocytes is required for effective support of neuronal activity and angiogenesis, while endothelial cells regulate bioavailability of lactate for brain cells adjusting its bidirectional transport through the BBB. In this article, we review the current knowledge with regard to energy production in endothelial and astroglial cells within the NVU. In addition, we describe lactate-driven mechanisms and action of alternative products of glucose metabolism affecting BBB structural and functional integrity in developing and mature brain.

The review covers current concepts on cell and molecular mechanisms of neuroinflammation and aging with the special focus on the regulation of cytokine-producing activity of astroglial cells and intercellular communication. The review reflects that a key component of the aging phenomenon as a result of ineffective implementation of anti-inflammatory response are processes of the dysregulated cytokine production, in particular, an increase in the secretion of proinflammatory cytokines and an imbalance in the expression of the receptors and receptor associated proteins. Interpretation of the molecular mechanisms of cell conjugating neuroinflammation and aging cells can give rise to new therapeutic strategies that are relevant to the treatment of a wide range of central nervous system diseases and the development of new experimental models of diseases of the central nervous system.

Impairment of hippocampal adult neurogenesis in aging or degenerating brain is a well-known phenomenon caused by the shortage of brain stem cell pool, alterations in the local microenvironment within the neurogenic niches, or deregulation of stem cell development. Environmental enrichment (EE) has been proposed as a potent tool to restore brain functions, to prevent aging-associated neurodegeneration, and to cure neuronal deficits seen in neurodevelopmental and neurodegenerative disorders. Here we report our data on the effects of environmental enrichment on hippocampal neurogenesis in vivo and neurosphere-forming capacity of hippocampal stem/progenitor cells in vitro. Two models - Alzheimer’s type of neurodegeneration and physiological brain aging – were chosen for the comparative analysis of EE effects. We found that environmental enrichment greatly affects the expression of markers specific for stem cells, progenitor cells and differentiated neurons (Pax6, Ngn2, NeuroD1, NeuN) in the hippocampus of young adult rats or rats with Alzheimer’s disease model but less efficiently in aged animals. Application of time-lag mathematical model for the analysis of impedance traces obtained in real-time monitoring of cell proliferation in vitro revealed that EE could restore neurosphere-forming capacity of hippocampal stem/progenitor cells more efficiently in young adult animals (4-fold greater in the control group comparing to the Alzheimer’s disease model group) but not in the aged rats (no positive effect of environmental enrichment at all). In accordance with the results obtained in vivo, EE was almost ineffective in the recovery of hippocampal neurogenic reserve in vitro in aged, but not in amyloid-treated or young adult, rats. Therefore, EE-based neuroprotective strategies effective in Aβ-affected brain could not be directly extrapolated to aged brain.

Communication consists of social interaction, recognition, and information transmission. Communication ability is the most affected component in children with autism spectrum disorder (ASD). Recently, we reported that the CD157/BST1 gene is associated with ASD, and that CD157 knockout (Cd157-/-) mice display severe impairments in social behavior that are improved by oxytocin (OXT) treatment. Here, we sought to determine whether Cd157-/- mice can be used as a suitable model for communication deficits by measuring ultrasonic vocalizations (USVs), especially in the early developmental stage. Call number produced in pups due to isolation from dams was higher at postnatal day (PND) 3 in knockout pups than wild-type mice, but was lower at PNDs 7 and 10. Pups of both genotypes had similarly limited voice repertoires at PND 3. Later on, at PNDs 7 and 10, while wild-type pups emitted USVs consisting of six different syllable types, knockout pups vocalized with only two types. This developmental impairment in USV emission was rescued within 30 min by intraperitoneal OXT treatment, but quickly returned to control levels after 120 min, showing a transient effect of OXT. USV impairment was partially observed in Cd157+/- heterozygous mice, but not in Cd157-/- adult male mice examined while under courtship. These results demonstrate that CD157 gene deletion results in social communication insufficiencies, and suggests that CD157 is likely involved in acoustic communication. This unique OXT-sensitive developmental delay in Cd157-/- pups may be a useful model of communicative interaction impairment in ASD. © 2017 Lopatina, Furuhara, Ishihara, Salmina and Higashida.

ВЛИЯНИЕ ИМПУЛЬСНОГО УЛЬТРАФИОЛЕТОВОГО ЛАЗЕРНОГО ИЗЛУЧЕНИЯ НА ФУНКЦИОНАЛЬНУЮ АКТИВНОСТЬ МАКРОФАГОВ В. В. Салмин, Д. П. Скомороха, М. Ю. Реушев, О. В. Фролова, Н. А. Малиновская , О. Л. Лопатина, А. Б. Салмина ГБОУ ВПО Красноярский государственный медицинский университет имени проф. В. Ф. Войно-Ясенецкого Министерства здравоохранения РФ, ректор – д. м. н. проф. И. П. Артюхов; кафедра медицинской и биологической физики, зав. – д. ф.-м. н. В. В. Салмин; кафедра биохимии с курсами медицинской, фармацевтической и токсикологической химии, зав. – д.м.н., проф. А. Б. Салмина; НИИ молекулярной медицины и патобиохимии; руководитель – д. м. н. проф. А. Б. Салмина.

Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis. Neurogenic niches represent the platform for tight integration of neurogenesis and angiogenesis supported by specific properties of cerebral microvessel endothelial cells contributing to establishment of partially compromised blood-brain barrier (BBB) for the adjustment of local conditions to the current metabolic needs of stem and progenitor cells. Here, we review up-to-date data on microvascular dynamics in activity-dependent neurogenesis, specific properties of BBB in neurogenic niches, endothelial-driven mechanisms of clonogenic activity, and future perspectives for reconstructing the neurogenic niches in vitro.

The transition to motherhood results in a number of hormonal, neurological and behavioural changes necessary to ensure offspring growth. Once motherhood is established, further neurological and behavioural changes may result in long-term memory in mothering. Recent research has shown that postpartum motherhood enhances both nurturing behaviour and oxytocin activities. The transmembrane glycoprotein, CD38, is expressed on many neuronal cells and has been shown to play a role in social behaviours through stimulating the release of oxytocin in the hypothalamus. The present study was performed to investigate the effects of reproductive experience (primi- and multiparity, dams and sires) on the degree of parental behaviour, such as retrieval. Comparisons were performed between wild-type (Cd38 (+/+) ) and Cd38 knockout (Cd38 (-/-) ) mice of the ICR strain. Multiparous Cd38 (-/-) dams retrieved pups much faster than primiparous mice, whereas there were no significant differences between primi- and multiparous Cd38 (+/+) dams. Plasma oxytocin levels were significantly increased in multiparous dams of both genotypes. In addition, oxytocin levels in the hypothalamus and pituitary were lower in Cd38 (-/-) than in wild-type mice. ADP-ribosyl cyclase activity in the hypothalamus, but not in the pituitary, was slightly increased in Cd38 (+/+) dams. In an identical test, 40% of first-time Cd38 (+/+) sires showed retrieval. The time required to retrieval was shorter in second-time Cd38 (+/+) sires. Both first- and second-time Cd38 (-/-) sires showed only 10% retrieval behaviour. These results indicate that parental behaviour is improved by reproductive experience, especially in Cd38 (-/-) dams, and suggest that these effects may be a result of increased oxytocin levels.

Alzheimer's type of neurodegeneration dramatically affects H2S and NO synthesis and interactions in the brain, which results in dysregulated vasomotor function, brain tissue hypoperfusion and hypoxia, development of perivascular inflammation, promotion of Aβ deposition, and impairment of neurogenesis/angiogenesis. H2S- and NO-signaling pathways have been described to offer protection against Alzheimer's amyloid vasculopathy and neurodegeneration. This review describes recent developments of the increasing relevance of H2S and NO in Alzheimer's disease (AD). More studies are however needed to fully determine their potential use as therapeutic targets in Alzheimer's and other forms of vascular dementia.

The peculiarities in expression of transport proteins and the proteins implicated in the control of glycolysis by the cellular components of neurovascular units were examined in animals of different age under normal conditions and after modeled perinatal stress or hypoxic brain injury. In both cases, the specialties in expression of transport proteins in ontogenesis were revealed. The perinatal hypoxic brain injury resulted in up-regulation of MCT1, MCT4, and GLUT4 expression in endotheliocytes of hippocampal microvessels accompanied by transient elevation of HIF-1α and GSK3 expression.

Neuroinflammation is as an important component of pathogenesis in many types of brain pathology. Immune mechanisms regulate neuroplasticity, memory formation, neurogenesis, behavior, brain development, cognitive functions, and brain metabolism. It is generally believed that essential homeostatic functions of astrocytes – astroglia-neuron metabolic coupling, gliovascular control, regulation of proliferation, and migration of cells in the neurogenic niches – are compromised in neuroinflammation resulting in excitotoxicity, neuronal and glial cell death, and alterations of intercellular communication. Viral neuroinfection, release of non-coding RNAs from the cells at the sites of brain injury or degeneration, and application of siRNA or RNA aptamers as therapeutic agents would require dsRNA-sensing pathways in the cells of neuronal and non-neuronal origin. In this review, we analyze the data regarding the role of astrocytes in dsRNA-initiated innate immune response in neuroinflammation and their contribution to progression of neurodegenerative and neurodevelopmental pathology.