Psychophysiological mechanisms of cognition disorders and optimization of their correction: I. Psychophysiological effects of transcranial micropolarization used as a corrective therapy for different disturbances in the control of wakefulness,emotions, and cognition in schoolchildren aged 10–12 years with learning difficulties

We have summarized the results of psychophysiological studies in schoolchildren aged 10–12 years with cerebral functional disturbances of hypoxic-ischemic or traumatic origin with learning difficulties. We have differentiated three types of disintegration of ultraslow information-controlling systems that reflect specific disturbances in the interaction of cortical-brainstem, limbic-reticular, and suprasegmental mechanisms of regulation of the wakefulness level and are characterized by emotional and cognitive disturbances typical of each type of disintegration. Adolescents with moderately and strongly decreased resistance to transitory hypoxia differed in psychological and psychophysiological effects of corrective and recovery therapy, which included transcranial micropolarization (TCMP) and psychological-pedagogical sessions during and between TCMP sessions and during the intervals between repeated TCMP courses. We discuss the psychophysiological mechanisms of the corrective effect of low-intensity direct currents with parameters close to the native ultraslow processes of the brain and the body systems regulated by these parameters.     

Intrasystemic and Intersystemic Rearrangements of Physiological Parameters in Experimental Acute Hypoxia

Simultaneous computer recording of the parameters of external respiration, systemic and cerebral blood circulation, arterial pressure, oxygen saturation of hemoglobin, and tissue oxygen tension has been used to study the intrasystemic and intersystemic rearrangements at different stages of acute hypoxia caused by breathing hypoxic oxygen–nitrogen mixtures containing 6.8–8.0% oxygen. It has been found that all main vital systems of the body are involved in the response to hypoxia; however, the degree of their involvement and the changes in individual parameters vary considerably in different subjects. The functional strain of some systems may remain almost constant throughout the period of hypoxia, whereas the strain of others may gradually increase or decrease. It has been found that each stage of hypoxia is characterized by certain limits of the strain (involvement) of the functional reserves of oxygen supply systems; if the functional strain goes beyond these limits, then either intrasystemic and intersystemic relationships are disorganized or compensation reserves are overspent and the time of tolerance to hypoxia is decreased.     

Human Systemic Reactions to a Dosed Exposure to Hypoxia: A Multiparameter Study

Human physiological reactions to acute hypoxic hypoxia were studied. Analysis of simultaneously recorded parameters of various physiological systems showed the following: activation of the general antihypoxic defense system is based on the formation of an intricate structure of intra- and intersystemic relations of specific and nonspecific elements of adaptation that support vital body functions during environmental oxygen deficit. These specific elements become more important in more severe hypoxia, which suppresses metabolism in some organs and tissues because of redistribution of blood flow. These factors allow the body to function at a lower oxygen tension in its tissues owing to an increased efficiency of mitochondria as a result of changes in the kinetics of enzymes of the mitochondrial respiratory chain. In acute hypoxia, the structure of intra- and intersystemic relations is rather intricate; its functional hierarchy is maintained by stronger individual amplitude-related controlling factors and by modulation of their phase- and time-related links. Advanced stages of hypoxia are associated with disintegration of central regulatory mechanisms, which is manifested by disturbances in amplitude-frequency and spatiotemporal parameters of the brain bioelectrical activity, changes in phasic interactions between elements of regulatory mechanisms, and signs of deregulation and decompensation of vital functions. The interpretation of the results is based on the general theory of adaptation, Medvedev's idea of adaptation as a successive involvement of genetically predetermined and newly-formed regulatory programs of the brain, Anokhin's theory of functional systems, and modern concepts of molecular and biochemical mechanisms of hypoxia. It was concluded that artificial normobaric hypoxia is a unique, biologically adequate model that makes it possible to study the rearrangements in systemic and autonomic regulatory mechanisms in response to strictly determined changes in the environmental concentration of oxygen as a principal factor supporting life.     

Problems of ecological lymphology

Ecological influences, exercised on one the most important homeostatic systems - the lymphatic system - have been investigated extremely insufficiently. Nevertheless, in mechanisms of adaptogenesis interaction of the environmental effects with the lymphoid organs plays a rather essential role. Structural-functional response of the lymph nodes to the environmental effects possesses some features of stereotype, however, the stereotypic response is subjected to modulations in connection with the factor acting and functional specialization of the lymph node. Keeping this in mind, the lymph nodes (their morpho-functional status) can be considered as markers of the environmental pressing to the lymphatic system. When estimating the degree and stage of the phasic morpho-functional changes in the lymph nodes during their adaptation to the environmental influences, it is necessary to take into account the possibility of the environmental (in our case - cooling, chemicals) imprinting, in order to judge on the degree of individual stability of the organism to these effects. The morpho-functional rearrangements in the lymph nodes, under the environmental influences on the animal organism, reflect the dynamics of complex interorganic correlations both within the lymphatic system and at intersystemic level.     

Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease

Abstract

Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and the organ systems that they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits, and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress (OS) appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and an instigator of OS, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models, by conserving myelin's structural integrity and alleviating functional deficits. This evidence indicates that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease.     

Psychophysiological condition of first-year students with different levels of physical activity

The psychophysiological condition of first-year students (males) going or not going in for sport in the course of training was investigated. Baevskii’s method was used to determine the level of stress of regulatory mechanisms. The functional level of the nervous system, the stability of neural responses, and the level of functional abilities of the developed functional system were evaluated using the variation chronoreflexometric method. It was established that an improvement in the mental capacity parameters (increased mental capacity, reduction in the number of errors, an increase in the level of functional abilities, and shortening of the latent period of visuomotor response) was accompanied by an increase of stress of the body regulatory systems, which was more marked in individuals with a low level of physical activity. This fact indicates that physical activity reduces the cost of the adaptation of the body to permanently changing environmental conditions. The optimal human adaptive systemic reactions are ensured by the dynamic interaction of the functional systems forming complex correlations in the somatic, autonomic, motor, and psychoemotional spheres of the body’s activity.     

Psychophysiological study of the effects of adaptation to tactile interaction with dolphins in six- to seven-year-old children

The possibility of the use of an integrative psychophysiological approach to the investigation of the role of ultraslow information-controlling brain systems in the mechanisms regulating the wakefulness level and the actual development of cognitive functions in six- to seven-year-old children was estimated. For the studied children, with different types of psychological adaptation to an unfamiliar emotional situation (tactile interaction with dolphins), we found the features of the development of (a) corticosubcortical and limbic-reticular mechanisms of regulation of the wakefulness level and (b) suprasegmental mechanisms of autonomic, hemodynamic, and oxygen-dependent energy supply of the wakefulness level. The idea of a correlation between (1) the level of actual emotional and cognitive development and the type of adaptation to psychoemotional stress and (2) age-specific features of the formation of reflex and neurohumoral mechanisms of regulation of the wakefulness level in six- to seven-year-old children is substantiated.     

Characteristics of the cerebral mechanisms controlling the level of wakefulness,maturity of cognitive functions,and adaptive responses in children with attention deficit hyperactivity disorder and healthy children of the same age

Data on the characteristics of the disturbance of ultraslow cortical-brainstem, limbic-reticular, and suprasegmental mechanisms controlling the wakefulness level (WL) in six- to seven-year-old children with attention deficit hyperactivity disorder (ADHD) and age-matched healthy children (first-year comprehensive primary school pupils) with different types of psychological adaptation have been summarized. An integrated systemic psychophysiological approach has been used to determine the characteristics of (a) the emotional-motivational and cognitive maturities and (b) the psychophysiological mechanisms of the formation of adaptive responses upon tactile interaction with an unfamiliar live object (a dolphin) in the examined groups of healthy and ADHD children.     

Peculiarities of interrelations of activation levels of frontal,temporal, and parietal cortex by parameters of ultraslow biopotentials in the 4–5-year-old children with the age norm and delayed speech development

Possibilities were considered of the integrative approach with use of parameters of the ultraslow informational-control brain and organism system in studying physiological grounds of the rest state, which determine structure and quality of the adaptive behavior. By using the proposal approach there were analyzed results of comparative studies of peculiarities of the wakefulness level, of its autonomous, hemodynamic, and oxygen-depended energy maintenance, and of activation levels and their interrelations in neocortical outputs of the brain systems of the frontal, temporal-parietal, and parietal cortex participating in organization of the higher integrative functions and speech in the 4–7-year-old children with the age norm of the general psychic and verbal development and with delay of the neuropsychic development, including development of speech.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 40, No. 5, 2004, pp. 455–468.Original Russian Text Copyright © 2004 by Ilyukhina, Krivoshchapova, Matveev, Ponomareva, Shaptilei.To the 100-Anniversary of N. N. Traugott     

Mechanisms of reference posture correction in the system of upright posture control

It was earlier shown that ultraslow tilts of the support under quiet standing conditions evoke an unusual response reflecting the operation of compensatory mechanisms: postural sway is a superposition of postural oscillations typical of quiet standing and greater, slower inclinations of the body caused by the tilt. This may be explained by the presence of two hierarchical levels of upright posture control: real-time control compensates for small deviations of the body from the reference posture prescribed by presetting control. Mathematical simulation methods have been used to study the mechanisms of reference posture control. The results are compared with available experimental data. It is demonstrated that the reference posture can be corrected according to the gravitational vertical with the use of a kinesthetic reference alone. It is hypothesized that, when correcting the reference posture, the nervous system “assumes” the support to be immobile. The afferent input from sole pressure receptors is an important factor in reference posture correction. The advantages of the putative two-level control over control based on an explicit internal model are discussed.     

Finding functions of phase separation in the presynapse

Synapses are the basic units of neuronal communication. Understanding how synapses assemble and function is therefore essential to understanding nervous systems. Decades of study have identified many molecular components and functional mechanisms of synapses. Recently, an additional level of synaptic protein organization has been identified: phase separation. In the presynapse, components of the central active zone and a synaptic vesicle-clustering factor have been shown to form liquid–liquid phase-separated condensates or hydrogels. New in vivo functional studies have directly tested how phase separation impacts both synapse formation and function. Here, we review this emerging evidence for in vivo functional roles of phase separation at the presynapse and discuss future functional studies necessary to understand its complexity.     

Association of enkephalin catabolism inhibitors and CCKB antagonists: A potential use in the management of pain and opioid addiction

The overlapping distribution of opioid and cholecystokinin (CCK) peptides and their receptors (μ and δ opioid receptors; CCK-A and CCK-B receptors) in the central nervous system have led to a large number of studies aimed at clarifying the functional relationships between these two neuropeptides. Most of the pharmacological studies devoted to the role of CCK and enkephalins have been focused on the control of pain. Recently the existence of regulatory mechanisms between both systems have been proposed, and the physiological antagonism between CCK and endogenous opioid systems has been definitely demonstrated by coadministration of CCK-B selective antagonists with RB 101, a systemically active inhibitor, which fully protects enkephalins from their degradation. Several studies have also been done to investigate the functional relationships between both systems in development of opioid side-effects and in behavioral responses. This article will review the experimental pharmacology of association of enkephalin-degrading enzyme inhibitors and CCK-B antagonists to demonstrate the interest of these molecules in the management of both pain and opioid addiction. Special issue dedicated to Dr. Eric J. Simon.     

Sex differences in microRNA regulation of gene expression: no smoke, just miRs

Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural) in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.     

Peptides as regulators of the immune system: emphasis on somatostatin

Study of the communication between nervous and immune systems culminated in the understanding that cytokines, formerly considered exclusively as immune system-derived peptides, are endogenous to the brain and display central actions. More recently, immune cells have been recognized as a peripheral source of “brain-specific” peptides with immunomodulatory actions. This article reviews studies concerning reciprocal effects of selected cytokines and neuropeptides in the nervous and immune systems, respectively. The functional equivalence of these two categories of communicators is discussed with reference to the example of the actions of neuropeptide somatostatin in the immune system.     

Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system

ABSTRACT: Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural) in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.     

Genes and homology in nervous system evolution: Comparing gene functions,expression patterns,and cell type molecular fingerprints

The evolution of the nervous system is one of the most fascinating, but also most nebulous fields of homology research. We do not know for example whether the last common ancestors of human, squid, and fly already possessed an elaborate brain and eyes, or rather had a simple, diffuse nervous system. Nevertheless, in the past decade molecular data has greatly advanced our understanding of bilaterian nervous system evolution. In this methodological review, I explain the four levels on which molecular genetic studies advance the quest for homologies between animal nervous systems. (I) Bioinformatic homology research elucidates the evolutionary history of gene families relevant for nervous system evolution such as the opsin superfamily. It tells us when and in what order genes and their functions have emerged. Based on this, we can (II) infer the organismal complexity of some remote ancestor from the functional diversity of its reconstructed proteome. (III) Most common in molecular homology research has been the comparison of expression patterns of developmental control genes. This approach matches and aligns embryonic regions along the body axes, between remote bilaterians. It does not tell us much, however, about the complexity of structures that developed from these regions in Urbilateria. (IV) This is overcome by a novel variant of molecular homology research, the comparison of cell types. Here, a similar “molecular fingerprint” of cells is taken as indication of cross-bilaterian homology. This approach makes it possible to reconstruct the cell-type repertoire of the urbilaterian nervous system.     

Effects of extremely high-frequency electromagnetic radiation on the immune system and systemic regulation of homeostasis

Low-intensity of electromagnetic radiation of extremely high frequencies (EHF EMR) is effectively used in medical practice for diagnostics, prevention and treatment of a broad spectrum of diseases of different etiology. However, in spite of existence of many hypotheses about mechanisms of EHF EMR effects on the molecular and cellular levels of organization of living systems, there is not conception that could explain all diversity of the EHF-therapy effects from unified approach. In our opinion, the problem of determination of mechanisms of EHF EMR effects on living organism is divided into two basic tasks: first, determining subcellular structures which can receive radiation, and, second, studying physiological reactions of the organism which are caused by radiation. It is obviously, that investigation of functions of single cells and subcellular elements can not entirely explain therapeutic effects and mechanisms of EHF EMR influence on multicellular organism on the whole. Plenty of functional relationships between organs and systems of organs should be taken into account. In the present review, a realization of the EHF-therapy effects due to the influence on immune system functions and start of system mechanisms of maintenance of the homeostasis on the organism level is hypothesized. Potential targets for EHF EMR acception on the level of different systems of the organism are analysed. The material is formed so that functional relations between immune system and other regulatory systems (nervous and endocrine systems) are traced.     

EvoD/Vo: the origins of BMP signalling in the neuroectoderm

The genetic systems controlling body axis formation trace back as far as the ancestor of diploblasts (corals, hydra, and jellyfish) and triploblasts (bilaterians). Comparative molecular studies, often referred to as evo-devo, provide powerful tools for elucidating the origins of mechanisms for establishing the dorsal-ventral and anterior-posterior axes in bilaterians and reveal differences in the evolutionary pressures acting upon tissue patterning. In this Review, we focus on the origins of nervous system patterning and discuss recent comparative genetic studies; these indicate the existence of an ancient molecular mechanism underlying nervous system organization that was probably already present in the bilaterian ancestor.     

Learning in sensorimotor circuits

The study of plasticity in the central nervous system is a major and very dynamic neuroscience research field with enormous clinical potential. Considerable advances in this field have been made during the past 10 years. It now appears that most circuits in the brain and spinal cord show plasticity and that they can be modified by experience. Knowledge of the mechanisms of plasticity in the nervous system is therefore essential for the understanding of how the nervous system is wired during development and how it adapts in response to changes in the body and environment. Recent findings indicate that functional sensorimotor modules probe the sensory signals from the body that are generated as a consequence of module specific activity and use this sensory feedback to calibrate the strength in its input-output connections. This experience-dependent signal adapts the circuitry in the sensorimotor module to the body anatomy and biomechanics.     

A psychophysiological analysis of the efficiency of instructing schoolchildren]

Examination of 163 schoolboys in higher forms has revealed that strength of the nervous system and functional state of the CNS (functional level of the system, level of functional possibilities, arousal and reaction stability) do not differ in schoolchildren with various progress in learning. The school teaching efficiency correlated with parameters of strength of the nervous system only in excellent and good pupils, the functional state of the nervous system being of importance for their teaching, especially its such parameters as arousal, level of functional possibilities and reaction stability. In pupils with poor progress those correlations were absent.