History of the mainstream scientific research at the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences

The classical reflex theory of the higher nervous activity has been developed in the works of E.A. Asratyan, the first director of the Institute, and his scientific school. The novel aspects of the theory have been developed: the principle of system organization; the concept of the nervous center as a set of structures located in different areas of the central nervous system; conditioned switchover, the mechanism of conditioned connection closure; the origin and localization of conditioned inhibition; the two-way, forward and backward conditioned connections. The elaboration of physiological mechanisms of the active goal-directed motivated behavior was begun. V.S. Rusinov and his collaborates have developed the concept of the dominanta and role of the stationary excitation foci in the integrative brain activity. M.N. Livanov has created the concept of the spatio-temporal organization of bioelectric potential and systemic organization of brain activity. P.V. Simonov, beginning from 1964, has developed the need-informational theory of the human and animal higher nervous activity (behavior). As distinct from the theories that originate from a single viewpoint and reject all the others, Simonov's theory is integrative and follows the logic of development of brain science.     

The effect of microwaves on the bioelectric brain activity

The experiments on rats have shown that the effect of millimeter range electromagnetic radiation on the bioelectric brain activity is dependent on the initial functional state of central nervous system. Microwaves are able to cause a nonspecific electroencephalographic reaction of synchronization and probably the lower the bioelectric brain process dynamics of active rats. Enrichment of electrocorticograms with high-frequency rhythms and increase in degree of bioelectric brain dynamics can be observed in narcosis conditions. The appearance of biological resonance in the brain of narcotized rats preliminary injected aminazin by pulse-modulated microwaves is noted. This is expressed as epileptiform convulsive activity in electrocorticogram. It has been shown that the nonlinear dynamics method may provide a reliable characterization of changing bioelectric brain activity under of nonionized electromagnetic fields. It is possible to modulate the bioelectric brain activity by microwaves to change the functional state of central nervous system and probably of the whole organism.     

Changes in metabolism of the nervous system in exposure to ionizing radiation at supralethal doses

Some biochemical disorders in the animals' central nervous system mainly in brain have been analysed after the exposure to superlethal doses of ionizing radiation as well in a state of the so-called early transient incapacity. The metabolism of gamma-aminobutyric acid, ammonia, histamine, cyclic nucleotides, prostaglandins and other biologically active substances is compared. Their investigation as metabolic regulators and modulators for nerve tissue seems to be of particular importance for deciphering the molecular mechanisms of changes in the central nervous system functional state and for discovering the possibility of its maintaining at a given level of activity.     

The brain renin-angiotensin system: a critical analysis.

The concept of a brain renin-angiotensin system originated with the observation that the components necessary for the formation of angiotensin II are present in the central nervous system. This observation has been confirmed and extended, and it is now frequently assumed that there is a functional brain renin-angiotensin system. However, careful analysis of the available evidence has revealed a number of significant problems. It appears that most of the renin-like activity measured in extracts of brain is due to the acid protease cathepsin D; this is unlikely to function as an angiotensin-forming enzyme in vivo. Experiments involving central administration of renin substrate have not provided convincing evidence for a significant renin-renin substrate interaction in vivo. Attempts to demonstrate the presence of angiotensin in the brain have been plagued with problems of specificity and it is still not clear if the peptide is actually present in the central nervous system. These problems do not rule out the possibility that there is a brain renin-angiotensin system, but more definitive evidence is required before it can be concluded that such a tensin system exists.     

Electroencephalogram-based anaesthetic depth monitoring in laboratory animals

Objective measurements of physiological parameters controlled by the autonomic nervous system such as blood pressure, heart rate and respiration are easily obtained nowadays during anaesthesia by the use of monitors: oscillometers, pulseoximeters, electrocardiograms and capnographs are available for laboratory animals. However, the effect-site of hypnotic drugs that cause general anaesthesia is the central nervous system (the brain). In the present, the adjustment of hypnotic drugs in veterinary anaesthesia is performed according to subjective evaluation of clinical signs which are not direct reflexes of anaesthetic effects on the brain, making depth of anaesthesia (DoA) assessment a complicated task. The difficulties in assessing the real anaesthetic state of a laboratory animal may not only result in welfare-threatening situations, such as awareness and pain sensation during surgery, but also in a lack of standardization of experimental conditions, as it is not easy to keep all animals from an experiment in the same DoA without a measure of anaesthetic effect. A direct measure of this dose-effect relationship, although highly necessary, is still missing in the veterinary market. Meanwhile, research has been intense in this subject and methods based on the brain electrical activity (electroencephalogram) have been explored in laboratory animal species. The objective of this review is to explain the achievements made in this topic and clarify how far we are from an objective measure of DoA for animals.     

The Functional State of Athletes Addicted to Exercises during Exercise Deprivation

The objective of this study is to identify markers of the addictive condition developing in athletes during exercise deprivation by analyzing electroencephalograms (EEGs), electromyograms (EMGs), skin temperature measurements, sympathetic nervous system activity, levels of anxiety and depression (by psychological tests). A cohort of professional football players (N = 50) voluntarily participated in the study. The athletes were tested under two test conditions: during active training sessions and during exercise deprivation (for seven days). The analyzed results have shown that the functional state of athletes with exercise addiction (due to exercise deprivation), compared with athletes showing no addictive behavior, was characterized by lower brain bioelectric activity (a decrease in the α-rhythm amplitude and power), growth in the muscular tension, increased sympathetic activity, and elevated levels of anxiety and depression. We have concluded that an athlete’s functional state during exercise deprivation is an important predictor for exercise dependence. A prolonged exercise deprivation causes intense psychophysiological changes in the body of athletes inclined to exercise addiction. The obtained results may be useful for experts in the field of sports medicine, as well as for further studies in different types of addictions.     

State of the antioxidant system during corazole kindling in rats

Antioxidation system was investigated in rats during kindling formation caused by daily administration of corazole in under-threshold doses. No changes have been observed in the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase and alpha-tocopherol content in the rat brain and blood. It is suggested that corazole-induced predisposition to epileptic activity is formed by mechanisms which are not associated with lipid metabolism in nervous tissue.     

Biochemical characterization of mouse d-aspartate oxidase

D-amino acids research field has recently gained an increased interest since these atypical molecules have been discovered to play a plethora of different roles. In the mammalian central nervous system, d-aspartate (D-Asp) is critically involved in the regulation of glutamatergic neurotransmission by acting as an agonist of NMDA receptor. Accordingly, alterations in its metabolism have been related to different pathologies. D-Asp shows a peculiar temporal pattern of emergence during ontogenesis and soon after birth its brain levels are strictly regulated by the catabolic enzyme d-aspartate oxidase (DASPO), a FAD-dependent oxidase. Rodents have been widely used as in vivo models for deciphering molecular mechanisms and for testing novel therapeutic targets and drugs, but human targets can significantly differ. Based on these considerations, here we investigated the structural and functional properties of the mouse DASPO, in particular kinetic properties, ligand and flavin binding, oligomerization state and protein stability. We compared the obtained findings with those of the human enzyme (80% sequence identity) highlighting a different oligomeric state and a lower activity for the mouse DASPO, which apoprotein species exists in solution in two forms differing in FAD affinity. The features that distinguish mouse and human DASPO suggest that this flavoenzyme might control in a distinct way the brain D-Asp levels in different organisms.     

Receptors for insulin-like growth factors in the central nervous system: structure and function

Insulin-like growth factors (IGFs) I and II are homologous peptides, which stimulate growth of several vertebrate tissues. Expression of IGF I and IGF II genes and production of IGFs have recently been demonstrated in rat and human brain. In search for the function of IGF I and IGF II in the central nervous system, we have studied IGF receptors in fetal and adult mammalian brain and growth effects of IGFs on primary cultures of fetal rat astrocytes. Two types of IGF receptor are present on adult rat brain cortical plasma membranes, on fetal rat astrocytes and on human glioma cells. Type I IGF receptor is composed of 2 types of subunits: alpha-subunits which bind IGF I and IGF II with high affinity and insulin weakly, and beta-subunits which show tyrosine kinase activity and autophosphorylation stimulated by IGF I and IGF II with almost similar potency. The molecular size of the type I IGF receptor alpha-subunit is larger in cultured fetal rat astrocytes and human glioma cells than in normal adult brain (Mr 130,000 versus 115,000), whereas the beta-subunit has the same electrophoretic mobility (Mr 94,000). The type II IGF receptor is a monomeric protein (Mr 250,000), which binds IGF II 5 times better than IGF I, and does not recognize insulin. The amounts of type II IGF receptor are significantly higher in fetal and malignant cells than in adult brain. Based on these findings we suggest that IGF receptors in brain undergo changes during fetal development and malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The experimental development of the concept of O. S. Adrianov on the correlation of functional and neurochemical processes: regulatory peptides in mediator system dysfunction

The article is devoted to commemoration of full member of Russian Academy of Medical Sciences, Oleg Andreevich Adrianov, who would have celebrated his 75-th anniversary in 1998. O. S. Adrianov, author of numerous works on physiology and morphology of central nervous system, in the recent years of his was studying the problem of the processes relationship at macro and micro levels of brain organization. Further to the concept created by O.S. Adrianov, data on action of two peptides: delta-sleep and tafcine, on behavior, neurophysiological and neurochemical processes have been consolidated. Experimental data were obtained for rabbits, cats, and dogs, both intact and in the state of pathology (psychomotoric excitement, bradykinesia, penicillin epilepsy). Impact of peptides on convergation processes is discussed: peptide of delta-sleep depresses reactions of brain structures to photo- and phono-stimulation, and activates the serotoninergic system in general; tafcine enforces the convergation processes and activates the dopaminergic system.     

Determination of Brain Death

With the careful application of the principles outlined herein, brain death can be determined with certainty. There have been no documented reports of survivors when these guidelines have been followed. The traid of a known mechanism of brain injury, absence of contributing metabolic or toxic central nervous system depression and absence of demonstrable brain function is sufficient to determine brain death clinically and, in most states, legally. The use of apneic oxygenation protects cadaver organs for transplantation during the period needed to prove that a patient cannot breathe.Very little can ameliorate the tragedy of sudden and unexpected fatal cerebral injury. Nonetheless, the concept of brain death is well established, and there is no longer a medical or an ethical reason to prolong unnecessary support of these patients.     

Periodic phenomenon in the ECoG of newborn rat pups and its correlation with spontaneous motor activity

In conscious 2-6-day rat puppies, studies have been made on the bioelectrical activity in the visual and sensorimotor cortex. ECG in newborn rat puppies exhibits characteristic intermittence of complexes of the electrical activity with intervals of partial or almost complete absence of the activity in a minute scale. This phenomenon reflects the ancient property of immature nervous system, i.e. a capacity to autogenic periodic excitation. The structure of these complexes may be different, since it reflects the condition of animals at the given moment, the degree of maturation of elements involved in realization of the bioelectrical activity and interrelationship with other parts of the brain. With respect to amplitude-frequency parameters, age dynamics and the relationship to the spontaneous motor activity, four distinct types of complexes were revealed in the ECG of rat puppies during the first week of their postnatal life.     

The effect of starvation during an early postnatal period on carbohydrate metabolism in the swine brain

Metabolism of carbohydrates in the brain of 110-day-feti, newborns (before taking the colostrum), 1-day-old and 5-day-old piglets, grown under sows or starved for 24 hours has been studied. Examination of brain slices with the use of 1-14C glucose and 6-14C glucose and determination of the glycolysis-limiting enzymes activity have shown that glycolysis is the main pathway of glucose utilization in the central nervous system of pigs during the transition from prenatal to postnatal development. The major portion of NADPH in the brain of new born piglets is supplied by dehydrogenases of the pentose-phosphate pathway. The increased activities of NADP-dependent malate and citrate dehydrogenases are found in the cytoplasm of astrocytes during the neonatal period. The decreased intensity of glycolysis and pentose-phosphate pathway in the brain of 1-day-old piglets is associated with the increased rate of malate and isocitrate oxidation. Starvation for 24 hours causes changes in the carbohydrate metabolism rates in the brain of piglets. The pentose-phosphate pathway rate increases by 70-80 per cent in the brain structures of piglets of the both groups. Besides, the iso-CDG activity also rises in the brain of 5-day-old animals. The high level of oxidation-reduction processes in the brain of older piglets at active glycolysis is supposed to be one of the peculiarities of energy metabolism in the central nervous system of animals which are resistant to starvation.     

Influence of cognitive load on the body functional state in children aged 9 to 12 years during early stages of puberty

This article analyzes heart rate variability (HRV), the glucocorticoid function of adrenal glands, and brain electrical activity (EA) in children aged 9 to 12 years to study their functional state during early stages of puberty. The cognitive load (mental arithmetic) caused low-frequency waves in the heart rate spectrum in all subjects, regardless of the puberty stage and gender. With respect to the age range under study, the hormonal response to the arithmetic test, expressed in a decrease in the level of cortisol, was observed in boys only at the third stage of puberty. The visual analysis of the background electrical encephalogram showed frequent generalized bilateral and synchronous changes in the electrical activity (EA) in the form of diencephalic signs in children. The features of the relationship between the autonomic nervous system and the hypothalamic pituitary-adrenal system have been revealed in children aged 9 to 12 years during cognitive load. The closest correlations between HRV indices and cortisol levels have been found in girls at the first stage and boys at the third stage of puberty.     

Neurobiology of exercise

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinson's disease, Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic responses to stress that could plausibly contribute to reductions in clinical disorders such as hypertension, heart failure, oxidative stress, and suppression of immunity. Mechanisms explaining these adaptations are not as yet known, but metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and the brain offer plausible, testable mechanisms that might help explain effects of physical activity and exercise on the central nervous system.     

FATTY ACID SYNTHETASE OF BRAIN: DEVELOPMENT, INFLUENCE OF NUTRITIONAL AND HORMONAL FACTORS AND COMPARISON WITH LIVER ENZYME

Abstract— The activity of fatty acid synthetase was studied in the brain and liver of the developing rat. Synthetase activity in brain was considerably higher in foetal and suckling rats than in older animals However, except for a small transient rise in the perinatal period, activity in liver was low until weaning when a dramatic rise occurred. Activity in brain varied according to the quantity of dietary fat only in long-term experiments, whereas in liver nutritional influences clearly predominated in determining the rapid developmental changes of synthetase activity. Administration of hydrocortisone diminished hepatic activity but did not change brain synthetase. In the hypothyroid state activity in brain and liver was consistently decreased. However, in the hyperthyroid state hepatic activity increased but activity in brain did not change. The relatively high activity of fatty acid synthetase during brain development has been discussed in relation to the critical role of this enzyme system in brain metabolism. The effect of the hypothyroid state on the activity of brain synthetase suggests the possibility of hormonal control of this enzyme activity. The responses of hepatic synthetase to the hormonal influences delineate a specific step by which these compounds may exert their effect on fatty acid biosynthesis.