Vol 111, No 1 (2025)

Microbiota and the macroorganism are in constant interaction with each other. Symbiotic microbiota participates in a number of important physiological, biochemical and neuroendocrine functions of the macroorganism. Metabolic activity of microbiota in the gastrointestinal tract (GIT) helps to digest food, absorb nutrients and extract energy. GIT microbiota participates in the metabolic processes of protein, fat and carbohydrate metabolism, in gluconeogenesis and glycogenolysis, and also affects the feeling of hunger and satiety. In addition, microbiota is often considered as a metabolically active "organ", since the power of metabolic reactions of the intestinal microbiota is comparable to that of the liver of the host organism. Microbiota produces autoinducers (quorum-sensing substances), hormones, neurotransmitters, short-chain fatty acids (SCFA), secondary bile acids, growth factors, gaseous molecules and many other active substances. Microbial metabolites provide the main communication between the host organism and its microbial community and are of great importance for the normal functioning of the macroorganism, starting from intrauterine development and ending with the aging process. Moreover, changes in metabolic activity and/or the ratio of different types of microorganisms can lead to various metabolic disorders of the host organism. Conversely, a metabolic disorder of the host organism can lead to a change in the species composition of the microbiota. This review describes the influence of the microbiota and its metabolites on the neuroendocrine functions of the macroorganism and describes the corresponding mechanisms of this influence.

Parkinson’s disease (PD) is an age-related neurodegenerative pathology characterized by abnormalities of the brain's dopaminergic system, alpha-synucleinopathy and motor dysfunction. Possible association of assisted reproductive technologies (ARTs) with neuropathologies is discussed in medicine literature, but there is a lack of experimental studies addressing this issue. The current study investigates the effects of ARTs, i.e. in vitro culture of preimplantation embryos and embryo transfer (ET) on the features characteristic for PD in offspring: motor dysfunction, decrease of neuronal density, e.g. density of dopaminergic neurons, as well as alpha-synuclein accumulation in substantia nigra pars compacta (SNpc). Male offspring of the B6.Cg-Tg strain and C57BL/6 strain (hereinafter referred as wild type, WT) obtained by ART (groups B6.Cg-Tg ET and WT ET) or by natural mating (groups B6.Cg-Tg CTL and WT CTL) were tested at the age of six months. Motor coordination and body balance were studied using the rotarod test; the density of neurons, as well as the accumulation of alpha-synuclein in the SNpc were assessed by immunohistochemical method. It was shown that B6.Cg-Tg mice obtained without ART (B6.Cg-Tg CTL) are characterized by the low density of neurons, including dopaminergic ones, as well as the accumulation of alpha-synuclein in SNpc as compared to wild type mice (WT CTL). Wild-type offspring obtained by ART (WT ET group) were characterized by the impairment in motor coordination and body balance, as well as by the decrease in the density of neurons in the SNpc, including dopaminergic ones. Offspring of the B6.Cg-Tg strain obtained by ART (B6.Cg-Tg ET group) were characterized by an increased accumulation of alpha-synuclein in the SNpc. The results of our study indicate possible association between using of modern reproductive technologies and predisposition to the neurodegenerative process and manifestations of the features characteristic to PD phenotype in offspring.

The microcirculatory bed is a crucial component of the cardiovascular system, at the level of which transcapillary metabolism occurs, which ensures the maintenance of body homeostasis. The analysis of changes in the mechanisms of microcirculation regulation depending on age is directly related to the development of predictive medicine.

Objective: To assess the dynamics of functional changes in microcirculation across different age groups and to identify the mechanisms of microcirculatory regulation in relation to age.

The study involved volunteers (from the city of Semenov) divided into three age groups. Group 1: 18–44 years old, group 2: 45–59 years old, Group 3: 60–74 years old. The work analyzed the normalized characteristics of the rhythms of blood flow fluctuations, studied the microcirculation index, indicators of oxidative and energy metabolism on the laser diagnostic device "LAZMA ST" (NPP "Lazma" LLC, Russia).

The study found that there was a decrease in the amplitudes of the endothelial rhythm (Ae), neurogenic rhythm (An) and heart rate (Ac) in group 2 compared to group 1, which was accompanied by an increase in microcirculation and increased oxidative metabolism. A further increase in perfusion and index of oxidative metabolism in group 3 caused a maximum decrease in the heart rate amplitude (As) and an increase in the endothelial (Ae), neurogenic (An) and myogenic (Am) amplitudes compared with groups 1 and 2. Energy metabolism indicators did not change significantly between the groups.

Thus, as people age there was an increase in the volume of blood entering the microcirculatory bed and an increase in oxidative metabolism, which was accompanied not only by changes in the reactivity of the cardiac component, but also an increase in the importance of local regulatory mechanisms in group 3.

In the present study, we investigated the neuroprotective effects of local therapeutic hypothermia (LTH) in a model of focal ischemia induced by epipial application of Endothelin-1 to the somatosensory cortex of the rat brain by morphometric analysis of ischemic foci formed 3 hours after Endothelin-1 application. The size of ischemic foci was measured in serial coronal brain slices after staining with 2,3,5-triphenyltetrazolium chloride (TTC). It was found that cooling the cortical surface to 28°C using a subdural Peltier element at 0, 10 and 60 minutes delay after Endothelin-1 application, caused a significant reduction in the size of ischemic focus compared to normothermic conditions. The neuroprotective effects of LTH were inversely correlated with the delay of LTH onset from the time of Endothelin-1 application and were most pronounced with LTH initiated with the shortest (0 and 10 minutes) delay after Endothelin-1 application. The size of the ischemic focus was also found to correlate significantly with the degree of electrical activity suppression analyzed in parallel paper. Taken together, the results of morphological and electrophysiological analysis indicate pronounced neuroprotective effects of surface LTH, particularly significant at minimal LTH latency after ischemic onset, in a model of Endothelin-1-induced focal ischemia in the rat cerebral cortex.

Long-term crowding in rats can lead to anxiety-depressive disorders. Antidepressants, including Imipramine, are used in clinical and experimental settings to correct such states. The aim of this study was to test whether Imipramine has an antidepressant and/or anxiolytic effect on the behavior of rats kept in overcrowded conditions. We studied the effect of daily (4 days before and 10 days during crowding) intraperitoneal injections of Imipramine at a dose of 10 mg/kg on the behavior in tests for anxiety (open field, light-dark, and elevated plus maze – EPM) and in forced swimming test after Imipramine withdrawal (12–15 days of overcrowding) in rats housed in overcrowded (16 rats per cage) and standard (4–5 rats per cage) conditions. Also, body weight gain on days 8 and 12 of overcrowding and the blood plasma corticosterone level on day 16 of overcrowding were assessed in the same groups of rats. Overcrowding led to activation of behavioral reactions in the light-dark and EPM tests, which did not decrease (with the exception of three indicators) after Imipramine treatment. So, Imipramine did not have a significant corrective effect in these tests on the behavior of rats kept in overcrowded conditions. In the forced swimming test under overcrowded conditions, an increase in immobility was observed, and imipramine led to the correction of this disorder. Body weight gain decreased after treatment of Imipramine in standard and overcrowded (to a greater degree) conditions, which may indicate a negative side effect of the antidepressant. The level of corticosterone in blood plasma did not differ in rats kept in overcrowded and standard conditions and did not change under the influence of Imipramine. Thus, the antidepressant Imipramine had a therapeutic effect on increased immobility in the forced swim test in rats under overcrowded conditions. This suggests that the behavioral changes observed in this test in rats under crowded conditions are depressive-like behavioral disorders. That is, imipramine had a pronounced antidepressant effect in the forced swimming test.

Neurodegenerative diseases are intricate pathological conditions characterized by the progressive degeneration and death of neurons in the nervous system. Consequently, researchers are increasingly focusing on strategies that utilize combinations of bioactive chemical compounds to convert other, more stable cell types into functional neurons. Chemical conversion has shown promise, particularly in models consisting solely of astrocytes; however, more realistic experimental systems include various cell types whose interactions may influence the response to chemical conversion. In this study, we investigated the impact of a multicomponent chemical cocktail on cells in mixed astro-neuronal cultures derived from the hippocampus of transgenic mice from the 5xFAD line, a genetic model of Alzheimer's disease (AD). Additionally, we recreated a model that simulates the reduction in ACE2 receptor activity observed in COVID-19 patients, which occurs due to internalization of the receptor after it binds to the coronavirus in order to study the consequences of chemical conversion upon disruption of this enzyme activity in the brain. Our findings indicate that the increase in neuronal density and the emergence of new neurons following exposure to the conversion cocktail in complex multicomponent cell systems become apparent only at later time points in cultures derived from non-transgenic animals, as well as in cultures from the 5xFAD mouse line. This may be attributed to the natural rise in astroglial levels during culture degradation. Notably, ACE2 inhibition significantly impacts the morphology of individual astrocytes and neurons. When we assessed the effects of the chemical cocktail, we observed that its efficacy was influenced by both the transgenic status of the culture and the timing of the conversion cocktail administration in relation to ACE2 inhibition. Cultures derived from transgenic animals exhibited higher susceptibility to both the ACE2 inhibitor and the chemical conversion agents.

The natural fear reflex, characteristic of both animals and humans, is a short and intense defensive reaction in response to a strong and unexpected external stimulus. In experiments, this reflex is often triggered by a strong and short sound stimulus (acoustic flinch reflex – ASR). The amplitude of the ASR and the degree of its dependence on modulating factors, such as a previous weak stimulus (prepulse), serve as markers of the state of sensorimotor gating and are widely used in neuropsychiatry and neurophysiology to assess disorders of mental functions. The magnitude of the ASR amplitude is a critical evaluation factor, and the accuracy of its determination depends on taking into account many technical conditions: the design of the experimental installation, the type and location of the mechanical-electrical sensor, the method of digitization and presentation of primary data, the protocol of the experiment, etc. This issue presents a methodological development for measuring ASR and its prepulse inhibition (PPI), which includes an original working camera, hardware and software, as well as an optimal testing protocol. During validation the technique on a group of outbred rats (Wistar), it was found that (1) the technique allows us to assess the heterogeneity of the group by the amplitude of ASR and conduct appropriate phenotypic clustering, and (2) repeated, after 7 days, testing of ASR and PPI in the same animals does not violate their initial clustering and does not significantly changes the measured parameters. These observations allow us to consider the methodology applicable for sequential testing of one group of animals before and after any experimental exposure, taking into account the dependence of the result on the cluster membership of the subgroups determined during the first test.