The effect of optical stimulation at a frequency of 10 Hz (OS10Hz) on temporal parameters of sensorimotor activity in healthy subjects (n=32) was studied. The expression of the activation response was determined by the ratio of spectral power values (SPα2, μV2) of the high frequency (10-13 Hz) subrange of the α-rhythm of the initial EEG with closed and opened eyes and the frequency of the maximum α-peak (IAPF). A test for simple motor reaction time was performed under normal and OS10Hz conditions. According to the change in the variability of simple motor reaction time (SDSMRT) under OS10Hz compared to the normal conditions, the subjects were classified into two groups: those who showed a decrease (group 1) and those who showed an increase (group 2) in SDSMRT. The subjects of group 1 had significantly higher IAPF (in the O1 lead with eyes closed) and activation reaction intensity (in the O2, O1, P4, P3, and F3 leads) compared to the subjects of group 2. The obtained data suggest that OS10Hz changes the parameters of psychomotor reactions of an individual, and the direction of changes is mediated by individual features of the initial EEG.
Aim: The aim of the study was to investigate changes in orienting and exploratory activity, anxiety level, eating and drinking behavior of female rats at different times after immunomodulation. Materials and methods: The experiments were performed on 22 female Wistar rats. Immunomodulation was carried out with the preparation Immunophan, which was administered subcutaneously on the 3, 5, 7, 9 and 11th days of observation. Behavioral studies in the elevated plus maze, as well as measurement of the amount of feed and liquid consumed were carried out on the 1, 13 and 26th days. Testing in the open field was carried out on the 2, 14t and 27th days. Results: Immunofan administration is accompanied by the formation of anxiety-like behavior in rats in relatively early terms, but by a decrease in anxiety at the late stage of observation. Animals receiving Immunofan are characterized by an increase in exploratory activity and suppression of eating behavior by the end of the experiments.
The parameters of the cytokine profile and functional activity of the complement system in the blood of rats were studied during different time periods of chronic unpredictable mild stress using a model of sequentially alternating low-intensity stress effects for 1, 2, 3, and 4 weeks. In the dynamics of observation, a general tendency towards multidirectional fluctuations in the concentration of cytokines was revealed: an increase in IL-10, but a decrease in IL-4 in comparison with the control. Statistically significant changes in the level of IL-10 were noted after 2, 3, and 4 weeks, IL-4 — after 2 and 4 weeks of stress loads. The percentage of lysis of the C3 component in rats gradually increased by the 2nd week of chronic stress, but then decreased and practically did not differ from the control values (intact animals) by the end of the study. These results illustrate the specificity of changes in the indicators of the C component of the complement system and the cytokine profile of the blood reflecting activity of the cellular and humoral components of the immune response in rats exposed to repeated stress factors of different origins and duration.
We studied interrelationships between behavioral parameters, metabolic processes, and cytokine content in the blood of male and female rats at different stages of postnatal ontogeny after intrauterine stress (mothers were forced to swim in cold water from the 10th to the 16th day of pregnancy). Correlations between behavioral and metabolic parameters in prenatally stressed rats were revealed at an earlier age (day 21 of life) than in controls. In comparison with intact rats, in males exposed to intrauterine stress no relationships between these parameters were revealed at older age, while in females, their direction and character change on day 60 of life. In prenatally stressed males, correlations of the blood levels of IL-6 were revealed: inverse relationships with behavioral parameters on the days 21 and 30 and direct relationships with metabolic parameters on day 60 of life. In prenatally stressed females on day 30 of life, we observed negative correlations between IL-4 levels and metabolic parameters that were absent under normal conditions. Thus, intrauterine stress leads to reorganization of the relationships between the parameters of metabolic and immune processes, which are essential for the purposeful behavior of mammals. The effects of stress seem to depend on the sex of the offspring and stage of postnatal development.
Длительные стрессорные воздействия вызывают дизрегуляцию большинства компонентов иммунной системы. Большой интерес исследователей к изучению системы комплемента и цитокинов связан с широким спектром их функций. Цель исследования – изучение показателей концентрации цитокинов и функциональной активности системы комплемента в крови крыс на модели хронического непредсказуемого мягкого стресса разной длительности. Методы. Исследование проведено на 42 крысах-самцах Wistar. Выделены 5 экспериментальных групп: контрольная группа; четыре опытные группы, которых подвергали многократным стрессорным нагрузкам на модели хронического непредсказуемого мягкого стресса в течение 1, 2, 3 и 4 недель соответственно. Концентрацию ИЛ-4 и ИЛ-10 в сыворотке крови крыс определяли методом твердофазного ИФА, функциональную активность системы комплемента – с помощью скрининг-теста в реакции комплемент-зависимого лизиса эритроцитов человека. Результаты. Выявлено статистически значимое повышение уровня ИЛ-10 через 2, 3 и 4 недели, но снижение концентрации ИЛ-4 в крови крыс через 2 и 4 недели стрессорных воздействий. Функциональная активность системы комплемента увеличивалась через 2 недели хронического стресса, но не отличалась от контрольных значений в последующие периоды. Заключение. Выявленные изменения иллюстрируют специфику активности клеточного и гуморального звеньев иммунного ответа в условиях многократных непредсказуемых стрессорных воздействий разной длительности. Long-term stress causes dysregulation of most components of the immune system. The great interest of researchers in studying the complement system and cytokines is associated with a wide range of their functions. The purpose of the study was to study the concentrations of cytokines and the functional activity of the complement system in the blood of rats using a model of chronic unpredictable mild stress of different durations. Methods. The study was conducted on 42 male Wistar rats. There were 5 experimental groups: control group; four experimental groups that were subjected to repeated stress loads in a chronic unpredictable mild stress model for 1, 2, 3 and 4 weeks, respectively. The concentration of IL-4 and IL-10 in the blood serum of rats was determined by solid-phase enzyme immunoassay, the functional activity of the complement system was determined using a screening test in the reaction of complementdependent lysis of human erythrocytes. Results. A statistically significant increase in the level of IL-10 was revealed after 2, 3 and 4 weeks, but a decrease in the concentration of IL-4 in the blood of rats after 2 and 4 weeks of stress exposure. The functional activity of the complement system increased after 2 weeks of chronic stress, but did not differ from control values in subsequent periods. Conclusion. The identified changes illustrate the specificity of the activity of the cellular and humoral components of the immune response under conditions of repeated unpredictable stressors of varying duration.
INTRODUCTION: Mammals are almost constantly exposed to a variety of stressors. The changes in the concentration of corticosterone and the level of glucose in blood of animals under such conditions seems relevant for understanding the influence of repeated stress effects on endocrine and metabolic processes. AIM: To study the concentrations of corticosterone and glucose in blood of rats in different time periods of prolonged low-intensity unpredictable stress. MATERIALS AND METHODS: Experiments were carried out on 42 male Wistar rats. Individuals of the experimental groups were subjected to 7-day cycles of alternating stressors using a modified model of chronic unpredictable mild stress with presentation of different stressors. The concentration of corticosterone and glucose in blood was determined at 1, 2, 3 and 4 weeks of observation. RESULTS: A pronounced decrease in corticosterone levels was found in rats at 1 week of stress exposure, followed by a slow recovery by the end of 4th week. Blood glucose level increased at 2 weeks of exposure. CONCLUSION: The data obtained illustrate the specificity of changes in the levels of glucose and corticosterone in the blood of mammals in different time periods of chronic stress. These changes characterize the dysregulation of the integrative physiological systems in relatively early periods of chronic stress with the subsequent development of adaptation in the later stages of repeated stress exposures.
Цель исследования: изучение перцептуального компонента болевой чувствительности, а также уровня тревожности и исследовательской активности самок крыс на модели дисфункции височно-нижнечелюстного сустава. Материалы и методы. Исследования проведены на 18 самках крыс Вистар. Дисфункцию височно-нижнечелюстного сустава (ВНЧС) моделировали при помощи внутрисуставного введения моноиодацетата натрия в дозе 16 мг/кг. В тесте «приподнятый крестообразный лабиринт» (ПКЛ) регистрировали общее время нахождения и количество заходов в закрытые или открытые рукава, число свешиваний и вертикальных стоек. Тестирование проводили в исходном состоянии и через 14 дней от начала опытов. Перцептуальный компонент ноцицепции животных изучали по латентному периоду отведения хвоста при свето-термальном раздражении методом «tail-flick». Измерения выполняли в фазу диэструса определяемой путем микроскопии вагинальных мазков. Болевую чувствительность оценивали в исходном состоянии, во 2-й и 3-й эстральный цикл после начала эксперимента. Результаты. Латентный период отведения хвоста крыс, получавших моноиодацетат натрия, при ноцицептивном раздражении снижался ко второму и третьему эстральному циклу по сравнению с исходным состоянием. В динамике наблюдений в ПКЛ для животных с дисфункцией височно-нижнечелюстного сустава характерно снижение времени выхода с центральной площадки, уменьшение числа вертикальных стоек и свешиваний по сравнению с исходным значением. В этих условиях выявлено, что крысы с болевым синдромом отличались от контрольных особей по следующим показателям: большей длительностью нахождения в закрытых рукавах, меньшим числом свешиваний. Заключение. Самки крыс с экспериментальной дисфункцией ВНЧС характеризуются усилением перцептуального компонента ноцицепции. Развитие болевого синдрома в челюстно-лицевой области сопровождается подавлением исследовательской активности и повышением уровня тревожности животных. The aim: to study the perceptual component of pain sensitivity, as well as the level of anxiety and exploratory activity of female rats on the model of temporomandibular joint dysfunction. Material and methods. Studies were conducted on 18 female Wistar rats. Temporomandibular joint (TMJ) dysfunction was modeled by intra-articular injection of sodium monoiodacetate at a dose of 16 mg/kg. In the elevated cruciate maze (ECM) test, total sitting time and number of entries into closed or open arms, number of overhangs and upright stances were recorded. Testing was performed at baseline and 14 days from the beginning of the experiments. The perceptual component of animal nociception was studied by the latent period of tail withdrawal during light-thermal stimulation using the “tail-flick” method. Measurements were performed in the diestrus phase determined by microscopy of vaginal swabs. Pain sensitivity was evaluated at baseline, in the 2nd and 3rd estrous cycle after the beginning of the experiment. Results. The latent period of tail withdrawal of rats receiving sodium monoiodacetate during nociceptive stimulation decreased by the second and third estrous cycle compared to the initial state. In the dynamics of observations of PCL, animals with temporomandibular joint dysfunction were characterized by a decrease in the time of exit from the central platform, a decrease in the number of vertical stands and overhangs compared to the initial value. Under these conditions, it was revealed that rats with pain syndrome differed from control individuals by the following parameters: longer duration of staying in closed arms, lower number of overhangs. Conclusion. Female rats with experimental TMJ dysfunction are characterized by strengthening of the perceptual component of nociception. The development of pain syndrome in the maxillofacial region is accompanied by suppression of exploratory activity and increased anxiety level of animals.
It has previously been shown that, in mice, chronic social defeat stress in daily agonistic interactions leads to a depression-like state similar to that in depressive patients. With this model, it has become obvious that it is possible to study peripheral markers of the depression-like state in an experiment. This paper was aimed at searching for protein markers in the blood plasma of depressed mice in the chronic social conflict model, which allows for us to obtain male mice with repeated experiences of defeat. Proteomic analysis of blood plasma samples was conducted to identify proteins differentially expressed in this state. There were changes in the expression levels of the amyloid proteins SAA1, SAA4, and SAMP and apolipoproteins APOC3, APOD, and ADIPO in the blood plasma of depressed mice compared with controls (unstressed mice). Changes in the expression of serine protease inhibitors and/or proteins associated with lipid metabolism, inflammation, or immune function [ITIH4, SPA3, A1AT5, HTP (HP), CO9, and A2MG] were also found. Here, we showed that chronic social stress is accompanied by increased levels of amyloid proteins and apolipoproteins in blood plasma. A similarity was noted between the marker protein expression changes in the depressed mice and those in patients with Alzheimer’s disease. These data indicate a psychopathogenic role of chronic social stress, which can form a predisposition to neurodegenerative and/or psychoemotional disorders.
INTRODUCTION: The aim of the work is analysis of one of the most important problems of the modern biomedical science problem of studying the processes of human adaptation to a complex of climatic and geographic factors and conditions of the Far North in the period of increased necessity in realization of the economic, industrial and defense activity of the government. The review presents the data of scientific study of cognitive functions and neurophysiological changes in people permanently living in or arriving to the Arctic zone. In the first part, the factors are considered that evidence different disorders in memory, concentration, efficiency of performing simple and complex cognitive tasks by test persons in conditions of low temperature, seasonal photoperiodicity, a particular working regime, such as rotational team method, etc. The age-related peculiarities of dynamics of the cognitive processes in children and adolescents living in the Arctic region are considered. The second part of the article presents analysis of scientific data on changes of electrophysiological parameters of the brain structure activity under the influence of individual or complex factors of Arctic conditions. In particular, changes of the encephalographic rhythms, evoked potentials, hemispheric asymmetry and parameters of autonomic regulation of the heart rate variability in the initial condition and on exposure to the factors of the Far North, are described. A necessity of individual typological analysis of the adaptation process characteristics depending on the initial regulatory peculiarities, neurophysiological characteristics of people, duration of their stay in the mentioned conditions, is emphasized. Inconsistency or ambiguity of the presented data indicate the importance of using a complex approach to scientific research which should include systemic analysis of the dynamics of neurophysiological characteristics and parameters of achieved effectiveness of modeled or professional activity in the Arctic conditions. CONCLUSION: The paper substantiates the necessity of elaboration of personalized methods of increasing the adaptive reserves of people working and living in the Arctic zones; one of these may be modern systems based on biocontrol with feedback from physiological systems of a human. Besides, it is noted that application of the principles of the theory of the functional systems formulated by academician P. K. Anokhin, can contribute to deeper understanding of adaptation processes, changes of cognitive and professional abilities, their neurophysiological support in the Arctic conditions.
We studied the effect of prenatal stress (dams were forced to swim in cold water (10°C; 5 min) from day 10 to 16 of gestation) on the behavioral parameters of the offspring in an elevated plus maze on days 21, 30, and 60 of life (suckling, infantile, and juvenile ages, respectively). Females at the suckling age demonstrated suppressed orientation and exploratory activity and increased anxiety, which returned to normal by the infantile and juvenile periods. Prenatally stressed males in juvenile age were characterized by reduced anxiety (assessed by the time spent in the closed and open arms of the plus maze). Thus, the effect of prenatal stress on the behavioral parameters manifested differently depending on the sex and stage of postnatal ontogeny. The modulatory effects of prenatal stress on the analyzed behavioral parameters were more pronounced in females at early stages of postnatal ontogeny (suckling and infantile ages).
The effectiveness of goal-directed human behavior and the processes underlying organization of such activity are the subjects of various biomedical studies. Here we review both classical and modern evidence on the fundamental principles of goal-directed human activity. Facts are presented about the basic mechanisms that ensure the effectiveness of goal-directed behavior and determine its physiological cost.
The concept of "useful adaptive result", a key concept in the theory of functional systems by P. K. Anokhin, is discussed. A large body of works devoted to this problem, in the historical aspect and on the basis of results of own researches, allows concluding that useful adaptive results of the system organization of physiological functions include not only the event arising as a result of activity of the system, but also the physiological cost of this activity. The ratio of the physiological cost and performance indicators gives an idea of the effectiveness of system activity and is its integral characteristic. The main approaches to estimation of physiological cost and efficiency of activity are discussed, as well as possibilities of using methods of applied mathematics (correlation and cluster analysis, artificial neural network technology) to describe system organization of physiological functions in healthy people. The question of the use of the proposed regulations to describe the system organization of physiological functions in patients with Parkinson's disease and epilepsy is considered.
We studied changes in the level of methylation of a number of microRNA genes hypermethylated in non-small cell lung cancer and its histological subtypes as well as the relationship of methylation of a group of microRNA genes with clinical and morphological features of the tumor with smoking status. A significantly high level of methylation of 7 genes (MIR124-1/3, MIR125B-1, MIR129-2, MIR137, MIR1258, and MIR339) was revealed in adenocarcinoma and squamous cell lung cancer in comparison with samples of adjacent histologically unchanged lung tissue. In squamous cell lung cancer, a significantly high level of methylation of the MIR124-2 gene in the tumor was also shown. In addition, differences in the methylation profile of adenocarcinoma and squamous cell carcinoma at stages III-IV of the oncological process were revealed. A high level of methylation of the MIR137 and MIR1258 genes was shown for adenocarcinoma and MIR339, MIR129-2, and MIR124-2 for squamous cell carcinoma. Significant differences in the level of methylation of MIR124-2 and MIR375 genes were revealed for smoking patients with squamous cell lung cancer.
We studied competitive interactions of rats during instrumental foraging behavior. Two groups of animals were revealed: rats with predominance of operant actions for getting food reinforcements (donors) and kleptoparasites that more often get food after instrumental acts of the partners. Intergroup differences began to appear and increased from 3-4 paired experiments. It was revealed that at the individual stage of learning the instrumental skill, donor rats were faster in learning and showed high foraging activity with shorter latency in comparison with kleptoparasites, which were initially slower and performed a large number of inter-signal actions in the form of unconditioned peeking into the feeder.
The effect of lateralized optical stimulation with a frequency of 10 Hz on the effectiveness of cognitive task performance (n-back test) was studied in 33 healthy subjects (right-handed men). Test visual information was presented to the right or left visual hemifield under normal conditions and against the background of optical stimulation with a frequency of 10 Hz. The absolute values of the spectral power of the high (10-13 Hz) subrange of alpha-rhythm of EEG (SPα2) were calculated. When test information was sent to the right hemisphere against the background of stimulation, an increase in task performance was revealed in subjects with low SPα2. This was accompanied by an increase in SPα2 in some cortical areas of the contralateral (left) hemisphere and, as a result, an increase in left-side dominance of SPα2. The findings indicate the possibility of using lateralized optical stimulation to improve cognitive task performance, in particular, by changing the interhemispheric asymmetry of the EEG alpha2-rhythm.
Parameters of blood cytokine profile in male and female rats subjected to prenatal stress on the model of swimming in cold water (10°C, 5 min, days 10-16 of gestation) were studied. Prenatal stress had no significant effects on the blood levels of IL-6 and IL-10 cytokines. The blood concentration of proinflammatory cytokine TNFα in 60-day-old rats was higher than in age-matched controls. Stress led to a lower level of anti-inflammatory IL-4 in the blood of 30-day-old males compared to controls. In female rats subjected to prenatal stress, the concentration of IL-4 decreased on day 21, but increased by day 60 of postnatal ontogeny. Specific effects of prenatal stress on the blood cytokine profile in male and female animals at different periods of ontogeny were revealed. Different and even opposite changes in blood cytokine levels could be largely mediated by sex- and age-specific features of immune functions after prenatal stress.
A change of pain sensitivity in rats of different sex and age (21st day, suckling period; 30th day, infantile period; and 60th day, juvenile period) was studied after prenatal stress of forced swimming in cold water. The perceptual component of nociception in prenatally stressed animals was shown to decrease on the 60th day of life compared to that in 21-day-old specimens. Importantly, the intensity of pain perception in juvenile rats subjected to intrauterine stress was smaller than control specimens. After prenatal stress, the emotional component of nociception in juvenile males and females was lower than in younger specimens. Therefore, prenatal stress is accompanied by a decrease in the perceptual and emotional components of nociception during the juvenile period, but not at the earlier stages of postembryonic development. The observed fluctuations in the degree of perception of the pain stimulus in male animals are slightly greater than those in females.