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The development of brain in vitro models requires the application of novel biocompatible materials and biopolymers as scaffolds for controllable and effective cell growth and functioning. The "ideal" brain in vitro model should demonstrate the principal features of brain plasticity like synaptic transmission and remodeling, neurogenesis and angiogenesis, and changes in the metabolism associated with the establishment of new intercellular connections. Therefore, the extracellular scaffolds that are helpful in the establishment and maintenance of local microenvironments supporting brain plasticity mechanisms are of critical importance. In this review, we will focus on some carbohydrate metabolites-lactate, pyruvate, oxaloacetate, malate-that greatly contribute to the regulation of cell-to-cell communications and metabolic plasticity of brain cells and on some resorbable biopolymers that may reproduce the local microenvironment enriched in particular cell metabolites.

The current prevalence of neurodevelopmental, neurodegenerative diseases, stroke and brain injury stimulates studies aimed to identify new molecular targets, to select the drug candidates, to complete the whole set of preclinical and clinical trials, and to implement new drugs into routine neurological practice. Establishment of protocols based on microfluidics, blood-brain barrier- or neurovascular unit-on-chip, and microphysiological systems allowed improving the barrier characteristics and analyzing the regulation of local microcirculation, angiogenesis, and neurogenesis. Reconstruction of key mechanisms of brain development and even some aspects of experience-driven brain plasticity would be helpful in the establishment of brain in vitro models with the highest degree of reliability. Activity, metabolic status and expression pattern of cells within the models can be effectively assessed with the protocols of system biology, cell imaging, and functional cell analysis. The next generation of in vitro models should demonstrate high scalability, 3D or 4D complexity, possibility to be combined with other tissues or cell types within the microphysiological systems, compatibility with bio-inks or extracellular matrix-like materials, achievement of adequate vascularization, patient-specific characteristics, and opportunity to provide high-content screening. In this review, we will focus on currently available and prospective brain tissue in vitro models suitable for experimental and preclinical studies with the special focus on models enabling 4D reconstruction of brain tissue for the assessment of brain development, brain plasticity, and drug kinetics., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

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., (Copyright © 2020 Lopatina, Komleva, Malinovskaya, Panina, Morgun and Salmina.)

Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin ( Oxt -/- , Cd38 -/- ) or its receptor ( Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Oxt -/- and Cd38 -/- , but not Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager -/- male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager -/- mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding., Competing Interests: The authors declare no competing interests.

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., (Copyright © 2018. Published by Elsevier Ltd.)

The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions. The release of gliotransmitters or cytokines by activated astroglial and microglial cells is provided by distinct mechanisms, affects intercellular communication, and results in the establishment of microenvironment controlling BBB permeability and neuroinflammation. Glial glutamate transporters and connexin and pannexin hemichannels working in the tight functional coupling with the purinergic system serve as promising molecular targets for manipulating the intercellular communications that control BBB permeability in brain pathologies associated with excessive angiogenesis, cerebrovascular remodeling, and BBB-mediated neuroinflammation. Substantial progress in deciphering the molecular mechanisms underlying the (patho)physiology of perivascular glia provides promising approaches to novel clinically relevant therapies for brain disorders. The present review summarizes the current understandings on the secretory machinery expressed in glial cells (glutamate transporters, connexin and pannexin hemichannels, exocytosis mechanisms, membrane-derived microvesicles, and inflammasomes) and the role of secreted gliotransmitters and cytokines in the regulation of NVU and BBB permeability in (patho)physiologic conditions.

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.

Connexins (Cx) play an important role in the coordination of intercellular communication, and autocrine and paracrine regulation of cells within the neurovascular unit (NVU). Gap junctional mechanisms control proliferation and differentiation processes underlying neurogenesis and angiogenesis in the brain. Cx43 possesses some unique properties [the ability to form either intercellular channels permeable for regulatory molecules and ions or hemichannels open to the extracellular space to provide release of cell metabolites; functional coupling with nicotinamide adenine dinucleotide (NAD+)-consuming and NAD+-dependent enzymatic processes] which may be of great importance for the fate of the stem cells. Dynamic changes in Cx43 expression are associated with different stages of brain cells development either at embryonic or adult periods of ontogenesis. This review summarizes recent data on Cx43-controlled neurogenesis in the context of NVU development and functioning. Understanding the molecular mechanisms of gap junctional intercellular communication will support translational studies focused on the development of regeneration-based approaches for the therapy of central nervous system pathology.

The aetiology of autism spectrum disorders remains unclear although a growing number of associated genetic abnormalities and environmental factors have been discovered in recent decades. These advancements coincided with a remarkable increase in the comprehension of physiological functions and pathological potential of neuroglia in the central nervous system that led to a notion of fundamental contribution of glial cells into multiple neuropathologies, including neuropsychiatric and developmental disorders. Growing evidence indicates a role for deregulation of astroglial control over homeostasis and plastic potential of neural networks as well as microglial malfunction and neuroinflammatory response in the brains of autistic patients. In this review, we shall summarize the status and pathological potential of neuroglia and argue for neuroglial roots of autistic disorders., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This review summarizes the literature and our own data regarding the role of NAD⁺-glycohydrolase/CD38-controlled molecular mechanisms of hypothalamic and pituitary oxytocin secretion in social behavior regulation. Current approaches to the modulation of both CD38 expression and brain cell activity that represent prospective treatments for disorders associated with altered social behavior are discussed.

There is growing evidence that the remodeling of cerebral microvessels plays an important role in plastic changes in the brain associated with development, experience, learning, and memory consolidation. At the same time, abnormal neoangiogenesis, and deregulated regulation of microvascular regression, or pruning, could contribute to the pathogenesis of neurodevelopmental diseases, stroke, and neurodegeneration. Aberrant remodeling of microvesselsis associated with blood–brain barrier breakdown, development of neuroinflammation, inadequate microcirculation in active brain regions, and leads to the dysfunction of the neurovascular unit and progressive neurological deficits. In this review, we summarize current data on the mechanisms of blood vessel regression and pruning in brain plasticity and in Alzheimer's-type neurodegeneration. We discuss some novel approaches to modulating cerebral remodeling and preventing degeneration-coupled aberrant microvascular activity in chronic neurodegeneration. [ABSTRACT FROM AUTHOR]

• Virtual reality (VR) and augmented reality (AR) systems are interactive tools for the establishment of alternative reality. • VR/АR application hаs been justified in terms of diagnostic, inhibition of age-associated or pathology-related processes. • VR/AR technologies provide new approaches to study neuroplasticity, complex behavior, and brain connectivity. 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. [ABSTRACT FROM AUTHOR]