In socially living species, including humans, social contacts’ deficit provokes chronic stress development, leading to disorders in the psychoemotional sphere, cognitive impairment, etc. Previously, we showed that spatial memory and passive avoidance impairments in rats exposed to months-long social isolation (SI) from an early age are more pronounced in females compared to males. There is lack research on females. This study aimed to evaluate learning in the two-way avoidance paradigm using the conditioned active avoidance reflex (CAAR) test and to assess skill retention in female rats exposed to SI, which started after the pups were taken from their dams and lasted for up to ten months. After 6.5 months of SI, rats were trained in the CAAR test when their anxiety level and grooming expression were lower than in rats housed in groups. Rats exposed to SI performed fewer avoidance but more escape responses and were less likely to achieve the learning criterion. In isolated rats compared to control rats, the escape latency was heightened, and the maximum number of avoidance reactions in a row was less after 24 hours after training. After 2 months after training, no differences in CAAR retention were revealed between rats kept in different housing conditions. After 10 months of SI, rat blood serum corticosterone levels were lower than in rats in the control group. The findings show worse learning and skill retention one day following training in the CAAR test in rats under the influence of long-term SI.

Childhood adversity can induce maladaptive behaviors and increase risk for affective disorders, post-traumatic stress disorder, personality disorders, and vulnerability to stress in adulthood. Deprivation of maternal care interrupts brain development through the disturbance of various neurotransmitters, however, the details remain unclear. The features of the symptoms of disorders are largely determined by early stress protocol, genetic characteristics (line), and the sex of the animals. The purpose of current study was (1) to assess behavioral changes in adult Wistar rats of both sexes after early life stress; (2) to determine the levels of monoamines in brain structures involved in the motor, emotional, and social reactions in rats aged 1 and 2 months; and (3) to determine the level of monoamines after physical or emotional stress in adult rats. The rat pups were separated from their dams and isolated from siblings in tight boxes at a temperature of 22–23 °C for 6 h during postnatal days 2–18. The data were processed predominantly using two-way analysis of variance and the Newman–Keys test as the post hoc analysis. The adult rats demonstrated an increase in motor activity and aggressiveness and a decrease in levels of anxiety and sociability. Behavioral disturbances were accompanied by region-, sex-, and age-dependent changes in the levels of monoamines and their metabolites. The dopaminergic and noradrenergic systems were found to be sensitive to psycho-emotional stress.

Summary. Monitoring of indicators of psychomotor coordination is used as a medical and biological support for innovations in the educational environment, to prove, at a minimum, the safety of pedagogical innovations for the health of students. With a broader approach, they study the absence of potentially pathogenic influences that can lead to alteration of both the physical and mental health of children. In this paper, we analyzed the results of testing the indicators of psychomotor coordination in students from the 1st to 4th grades: 2677 girls and 1528 boys; a total of 4205 children from 66 schools. Some of the surveys were carried out in the fall (early October), some in the spring (March-April). Psychomotor parameters were assessed based on the results of performing motor tests on a computerized movement meter (CMM) when performing movements in the elbow joint. The speed, accuracy and smoothness of movements, the time for changing the motor stereotype, and sensorimotor reactivity to stimuli of different modalities (light and sound) were assessed. It is shown that during 4 years of education in primary school there is an improvement in speed and accuracy indicators of psychomotor, smoothness of movements, as well as an increase in sensorimotor reactivity, however, the time for changing the motor stereotype increases (dexterity decreases), which may reflect the transition to a new paradigm of motion control. For all indicators, the following was found: 1) the presence of age dynamics (by class), 2) statistically significant differences in the dynamics of the results of autumn and spring surveys, 3) differences between girls and boys. Consequently, a correct assessment of potentially pathogenic effects on a growing organism can be carried out only in the same season.

Chronic stress due to social isolation (SI) can lead to distress with negative consequences for both humans and animals. Numerous disorders caused by SI include disorders in the emotional-motivational domain and cognitive functions, as well as changes in social behavior. There are currently no data identifying the sequelae of SI when its duration is significantly increased. Although female rats have been shown to be highly sensitive to stress, research on them is lacking. The present study assessed sociability and preference for “social novelty” in a three-chamber social test in female Wistar rats in two series of experiments at different time points during prolonged SI, which began at adolescence and continued to ages 5.5 and 9.5 months. At two months of SI, rats showed an increased preference for a social object over a non-social object (increased sociability) simultaneously with the appearance of signs of a decrease in the preference for a new social object over an already familiar social object (signs of a decrease in the preference for social novelty). In a social interaction test, the rats also displayed increases in the durations of social contacts, including aggressive interactions; they showed a decrease in exploratory risk assessments (head dips from the open arms) in the elevated plus maze test and a decrease in exploratory activity. After SI lasting 8.5 months, the rats showed signs of social deficit and a marked decrease in the preference for social novelty. No signs of increased aggressiveness were found. Thus, the impact of SI on social behavior depended on its duration and, we believe, was accompanied by a change in coping strategies.

Social isolation (SI) is chronic psycho-emotional stress for humans and other socially living species. There are few comparative studies that have measured monoamine levels in brain structures in male and female rats subjected to SI. Existing data is highly controversial. In our recent study, we investigated behavioral effects of SI prolonged up to 9 months on a rather large sample of 69 male and female Wistar rats. In the present study, we measured the levels of monoamines-norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), and DA and 5-HT metabolites-in the brain structures of 40 rats from the same sample. The single-housed rats of both sexes showed hyperactivity and reduced reactivity to novelty in the Open Field test, and impaired passive avoidance learning. Regardless of their sex, by the time of sacrifice, the single-housed rats weighed less and had lower pain sensitivity and decreased anxiety compared with group-housed animals. SI decreased NE levels in the hippocampus and increased them in the striatum. SI induced functional activation of the DA-ergic system in the frontal cortex and hypothalamus, with increased DA and 3-methoxytyramine levels. SI-related changes were found in the 5-HT-ergic system: 5-HT levels increased in the frontal cortex and striatum, while 5-hydroxyindoleacetic acid only increased in the frontal cortex. We believe that SI prolonged for multiple months could be a valuable model for comparative analysis of the behavioral alterations and the underlying molecular processes in dynamics of adaptation to chronic psychosocial stress in male and female rats in relation to age-dependent changes.

Silver nanoparticles (AgNP) are known to penetrate the brain and cause pathological changes in central nervous system (CNS) functions. Still, it remains unclear whether AgNP solutions as antimicrobial agents are safe for humans. The attempt was undertaken to assess the risk of commercial silver nanoparticles for CNS, using a rat as a model and creating conditions as close as possible to human intake of aqueous AgNP solutions. The silver nanoparticle solutions prepared with natural stabilizer were used, a low dosage (51 μg/kg), intake with drinking water, and long-time exposure. We determined the effect of the AgNP solution on some indices of animal behavior—motor activity, anxiety, and short-term habituation (non-associative learning)—1 and 2 months after the start of the consumption and three months after the AgNP withdrawal. After the 2-month course, rats showed (1) an increase in motor activity and a decrease in anxiety-phobic levels under a stressful environment of a classic open field test, (2) a lack of short-term habituation in the acoustic startle, and (3) presence of the nanoparticles in the hippocampus, frontal cortex, and striatum as detected by transmission electron microscopy. These signs disappeared three months after the AgNP withdrawal. The results suggest that under experimental conditions close to actual human consumption, silver nanoparticles do not have a long-term adverse effect on the CNS functions.

Все большее значение для исследований в экстремальных условиях и при моделировании космических полетов приобретает комплексная оценка сердечно-сосудистой вариабельности, которая помимо вариабельности сердечного ритма включает в себя оценку вариабельности артериального давления. Использование спироартериокардиоритмографов (САКР) позволяет синхронно регистрировать работу проводящей системы сердца (ЭКГ), артериальное давление (АД) и дыхание, а также автоматически оценивать вариабельность ритмических осцилляций частоты сердечных сокращений и периферического АД. Материалы и методы. В этой работе мы анализировали напряженность регуляции сердечно-сосудистой системы организма человека при 21-дневной антиортостатической гипокинезии (АНОГ) на приборах САКР разных поколений, оценивая их релевантность для такого анализа. Результаты. В работе показано, что измерения на приборе САКР выявляют значимое снижение общей вариабельности АД вследствие длительной моделированной микрогравитации. Причём основной вклад в эти изменения вносит очень низкочастотная составляющая вариабельности систолического АД (VLFs). Известно, что именно VLF-компонента вариабельности АД может служить показателем предрасположенности к инсультам у крыс и собак, и, предположительно, может иметь прогностическое значение для оценки вероятности развития инсультов у человека. Заключение. Результаты этой работы говорят о большой важности адекватной оценки вариабельности АД с помощью неинвазивных приборов типа САКР для выявления и оценки преморбидных состояний, а также исследований адаптации при стрессе и в экстремальных условиях космических полетов. A comprehensive assessment of cardiovascular variability, which includes an assessment of blood pressure (BP) variability in addition to heart rate variability, is becoming increasingly important for research under extreme conditions, i.e., space, and during modeling of space flight. The use of spiroarteriocardiorhythmographs (SACR) allows synchronous recording activity of the cardiac conduction system (ECG), BP, and respiration, as well as automatic assessment of the variability of rhythmic oscillations of heart rate and peripheral BP. Methods. We analyzed the intensity of regulation of the human cardiovascular system during 21-day antiorthostatic hypokinesia (ANOH) using SACR devices of different generations, and we assessed their relevance for such an analysis. Results. Measurements on the SACR device revealed a significant decrease in the overall BP variability due to prolonged, simulated microgravity. Moreover, the main contribution to these changes was made by the very low-frequency component (VLF) of systolic BP variability. It is known that specifically the VLF component of BP variability indicates a predisposition to strokes in rats and dogs, and quite possibly it has a prognostic value for assessing the risk of stroke in humans. Conclusion. These results suggest adequate assessment of BP variability using non-invasive devices (e.g. SACR) is very important for the identification and assessment of premorbid states and can be applied to studies of adaptation to the stress and extreme conditions of space flights.

Early-life stress is a risk factor for the development of behavioral and cognitive disorders in humans and animals. Such stressful situations include social isolation in early postnatal ontogenesis. Behavioral and cognitive impairments associated with neuroplastic changes in brain structures. We have found that after ten weeks of social isolation, male Wistar rats show behavioral abnormalities and cognitive deficit, accompanied by an increase in the relative expression of gene encoding serine protease prolyl endopeptidase (PREP, EC 3.4.21.26) in the brain frontal cortex. The present study aimed to assess synaptophysin (SYP), brain-derived neurotrophic factor precursor (proBDNF), and PREP expression using Western blot in the brain structures – the hippocampus, frontal cortex, and striatum of the rats subjected to prolonged social isolation compared with group-housed animals. Twenty Wistar rats were used for this study (10 males and 10 females). Experimental animals (5 males and 5 females) were kept one per cage for nine months, starting from the age of one month. Ten-month-old socially isolated rats showed memory deficit in passive avoidance paradigm and Morris Water Maze and reactivity to novelty reduction. We used monoclonal antibodies for the Western blot analysis of the expression of SYP, proBDNF, and PREP in the rat brain structures. Social isolation caused a proBDNF expression reduction in the frontal cortex in females and a reduction in PREP expression in the striatum in males. These data suppose that neurotrophic factors and PREP are involved in the mechanisms of behavioral and cognitive impairments observed in the rats subjected to prolonged social isolation with an early life onset.

Введение. Ингибиторы пролинспецифической сериновой протеазы дипептидилпептидазы IV (ДПП-IV, CD26, EC 3.4.14.5), способные модулировать широкий спектр физиологических процессов, находят применение в клинике. В наших работах получены свидетельства влияния ингибиторов ДПП-IV при их введении в раннем постнатальном периоде на эмоционально-мотивационное поведение взрослых крыс. Более сильные изменения в поведении отмечались у крыс при действии ингибитора ДПП-IV дипротина А. Однако не ясно, как долго сохраняются такие изменения. Цель работы - изучение отсроченных эффектов ингибитора ДПП-IV дипротина А на выраженность эмоционально-мотивационных расстройств, индуцированных действием ингибитора в раннем постнатальном периоде, в динамике взросления крыс от 2 до 7 мес. Методика. Дипротин А вводили крысятам ежедневно в 5-18-й постнатальные дни внутрибрюшинно (2 мг/кг), в объеме 0.1 мл на 10 г массы тела. Крысята контрольной группы получали инъекции физиологического раствора. Поведение взрослых крыс оценивали в возрасте 2 и 7 мес в тестах автоматизированного «открытого поля», «Приподнятый крестообразный лабиринт» (ПКЛ), принудительного плавания и социального взаимодействия. Уровень кортикостерона в сыворотке крови определяли методом твердофазного иммуноферментного анализа ELISA. Для статистической обработки результатов использовали двухфакторный дисперсионный анализ Two Way ANOVA и непараметрический U-критерий Манна-Уитни с поправкой на множественность сравнений. Результаты. У крыс опытной группы по сравнению с контрольной группой в возрасте 2 и 7 мес была повышена двигательная активность и скорость перемещения в тесте ПКЛ. В возрасте 7 мес у них также была увеличена вертикальная исследовательская активность. Признаков повышения тревожности не выявлено. У крыс опытной группы выявлены признаки депрессивно-подобного поведения по нарушению биоритмологической структуры плавания, более выраженные в возрасте 7 мес. Неагрессивное социальное взаимодействие у крыс, получавших неонатально дипротин А, было снижено по сравнению с контролем в возрасте 2 мес, а в возрасте 7 мес, напротив, увеличено. У этих животных число и длительность агрессивных социальных контактов были увеличены по сравнению с контролем как в возрасте 2, так и в возрасте 7 мес. Уровень кортикостерона в сыворотке крови у крыс опытной группы в возрасте 7.5 мес был выше, чем в контроле. Заключение. Данные настоящего исследования свидетельствуют о развитии гиперактивного фенотипа и длительных психоэмоциональных нарушений в виде повышенной агрессивности наряду с активацией гипоталамо-гипофизарно-адреналовой оси у взрослых крыс, подвергнутых действию дипротина А в 5-18-й постнатальные дни, и поддерживают представления об участии дипептидилпептидазы-IV в генезе психоэмоциональных расстройств. Background. Inhibitors of the proline-specific serine protease dipeptidyl peptidase IV (DPP-IV, CD26, EC 3.4.14.5) may modulate a wide range of physiological processes and are used in the clinic. In our studies, we obtained evidence for the impact of DPP-IV inhibitors on adult rats’ emotional and motivational behavior when administered in the early postnatal period. Diprotin A exhibited the most significant impact on the animals’ behaviors. However, it is not clear how long the changes persist. Aim. To study the delayed effects of the DPP-IV inhibitor diprotin A on the severity of emotional and motivational disorders induced by the inhibitor action in the early postnatal period, in the dynamics of rats maturation from 2 to 7 months. Methods. Diprotin A was administered to rat pups daily on postnatal days 5-18, intraperitoneally, at a dose of 2 mg/kg, in a volume of 0.1 ml per 10 g of body weight. The rat pups of the control group received saline. The behavior of adult rats was assessed at the age of 2 and 7 months in the automated “open field,” “Elevated Plus Maze” (EPM), forced swimming, and social interaction tests. Serum corticosterone levels were determined by ELISA. The results were statistically processed using Two Way ANOVA and nonparametric Mann-Whitney U-test adjusted for multiple comparisons. Results. Experimental rats increased motor activity and travel speed in the EPM test compared with the control group at 2 and 7 months of age. At the age of 7 months, experimental rats also increased vertical (rearing) activity. There were no signs of increased anxiety. Experimental rats demonstrated depression-like behavior judged by the biorhythmologic structure of swimming, more pronounced at 7 months. Non-aggressive social interaction in rats treated neonatally with diprotin A was reduced compared with controls at the age of 2 months and, on the contrary, increased at the age of 7 months. In these animals, the number and duration of aggressive social contacts were increased compared with controls at the ages of 2 and 7 months. Serum corticosterone levels in experimental rats at the age of 7.5 months were higher than in control. Conclusion. The present study results testify to the development of a hyperactive phenotype and prolonged psychoemotional disorders as increased aggressiveness along with hypothalamic-pituitary-adrenal axis activation in adult rats exposed to the action of diprotin A on postnatal days 5-18. The data support the dipeptidyl peptidase IV involvement in the genesis of psychoemotional disorders.

Indicators of the cardiovascular system, including heart rate (HR) and blood pressure (BP) variability parameters, were analyzed in primary school students with different computer screen times. The study included 4084 students of grades 1–4 (age 7–12 years) from 66 Moscow schools. The screen time at school and out of school was assessed by teachers, based on the national Sanitary Rules and Regulations: 0, no screen time; 1, screen time matching hygienic standards; 2, screen time at least twice greater than recommended. Physiological examinations were carried out by spiroarteriocardiorhythmography with a face mask, the conditions corresponding to the functional stress test (mild hypercapnia/hypoxia). Testing took place in spring and autumn (independent samples). Statistical data processing was performed using nonparametric criteria. It was revealed that the introduction of computer technologies in school lessons within the limits of hygienic standards was accompanied by an increase, within the normal range, of systolic BP in girls at the end of grade 2 and 4 and in boys at the beginning and end of grade 4. Screen time at least twice higher than the hygienic standard did not have an additional effect on BP, but provoked shifts in the function of autonomic regulation. Boys were more sensitive to the influence of this environmental factor. Their pattern of seasonal variability in total power (TP) of the HR variability spectrum was reversed compared to that of children who did not use computers at school; i.e., higher TP values were observed in spring. In grade 4, the process was accompanied by an increase in spontaneous arterial baroreflex sensitivity and a decrease in the relative power of the LF range in the variability spectrum of systolic BP. The changes were assumed to reflect the adaptive response to changes in educational environment.

The levels of monoamines and their metabolites in the brain structures of adult Wistar rats subjected to post-weaning social isolation for 2 and 3 months were analyzed by HPLC with electrochemical detection. We have previously shown that these rats consistently demonstrate increased aggressiveness and, as a rule, impairment of short-term habituation. Two-monthlong social isolation was accompanied by a reduction in serotonin content and its increased turnover judging from the 5-HIAA/5-HT ratio in the hippocampus; three-month-long isolation was associated with increased levels of serotonin and reduction in its turnover in the amygdala. At this term, the level of dopamine metabolite 3-methoxytyramine tended to increase in the amygdala. In the frontal cortex, a tendency to a decrease in 5-HT level was found. These findings suggest that more prolonged post-weaning social isolation is accompanied by reorganization of neural networks in the brain cortex, which can serve as the pathophysiological basis for psychoemotional disorders.

Background: The chronic stress of social isolation is a valid predictor of cognitive pathology. This study aimed to compare the effects of long-term social isolation on female versus male Wistar rats' learning and memory. We hypothesized that prolonged social isolation stress, which starts early in life, would affect learning in a sex-dependent manner. Methods: Social isolation started at the edge of early to mid-adolescence and lasted 9 months. The rat's cognitive abilities were assessed by habituation and reactivity to novelty in the open field (OF) test, spatial memory in the Morris water maze (MWM), and the conditioned passive avoidance (PA) reflex. Basal serum corticosterone levels were assessed using an enzyme-linked immunosorbent assay. Results: Regardless of the housing conditions, females habituated to the OF under low illumination slower than males. Under bright light, the single-housed rats showed hyporeactivity to novelty. In the MWM, all the rats learned to locate the platform; however, on the first training day, the single-housed females' speed was lower relative to other groups. Four months later, in the post-reminder probe trial, the single-housed rats reached the area around the platform site later, and only males, regardless of housing conditions, preferred the target quadrant. Single-housed rats, irrespective of sex, showed a PA deficit. There was a more pronounced conditioned fear in the single-housed males than in females. In both male and female rats, basal corticosterone levels in rat blood serum after 9 months of social isolation did not differ from that in the group-housed rats of the corresponding sex. Meanwhile, females' basal corticosterone level was higher than in males, regardless of the housing conditions. The relative weight of the adrenal glands was increased only in single-housed females. Conclusions: Under long-term social isolation, started early in life, single-housed females compared with males showed more pronounced cognitive impairments in the MWM and PA paradigm, findings that specify their greater vulnerability to the stress of prolonged social isolation.