Vol 110, No 5 (2024)

Ischemic stroke (IS) is a prevalent condition with high mortality and disability risks worldwide. As of now, the issue of pathogenetic therapy remains unresolved due to the limited effectiveness and safety of reperfusion measures. Recent research has elucidated that neuroinflammation plays a pivotal role in IS development and may serve as a therapeutic target. The NLRP3 inflammasome emerges as a key mediator orchestrating post-ischemic inflammatory reactions through the activation of caspase-1, which cleaves pro-interleukin-1 beta and -18 precursors into active proinflammatory cytokines released into the extracellular milieu. This review presents insights into the structure and activation process of the NLRP3 inflammasome in IS. Factors and mechanisms contributing to both its activation and inhibition are delineated.

The article analyzes literature data on the close relationship between energy balance and sense of smell. Olfaction is one of the main modalities of hedonic evaluation of food. Odor is one of the most important sensory signals predicting food quality and plays a key role in food selection and consumption. Appetite can be stimulated by various stimuli, but the leading role belongs to olfactory signals (tasty smells) and levels of hormones that signal hunger and satiety. Olfactory perception is subject to hormonal modulation. In this regard, special attention in the article is paid to the modulating function of insulin. Insulin, one of the main metabolic hormones that controls food intake, has an anorexigenic effect not only at the level of the hypothalamus, but also at the level of the olfactory pathway, especially strong in the olfactory bulb. It has a rate of insulin transport two to eight times higher than in other parts of the brain, and it contains the highest concentration of insulin and the highest density of insulin receptor kinase. Thus, insulin is not only able to penetrate to the site of olfactory information processing, but do so quickly. At the same time, insulin and its receptors are localized in the olfactory epithelium, namely in mature olfactory sensory neurons. Therefore, insulin affects the primary stage of perception of an odorous molecule – odor detection, which occurs at the level of the olfactory epithelium. The sense of smell is impaired up to its complete loss in obesity and type 2 diabetes, worsening the quality of life of such patients. The paper examines the effectiveness of intranasal insulin administration to restore olfactory function in metabolic disorders and other diseases.

Prolonged bed rest can have a significant negative effect on skeletal muscle, leading to muscle wasting and reduced strength. This process can occur in as little as 10 days in healthy individuals, with the loss of muscle mass and strength being particularly pronounced during the first week of immobilization. Head-down tilt bed rest (HDT) is a method used to simulate the physiological changes that occur in weightlessness during spaceflight. This technique involves lying in bed with the head tilted downward. This paper is dedicated to the analysis of key anabolic markers of the soleus muscle during 21 days of HDT BR. The HDT BR experiment was conducted at the Institute of Biomedical Problems, Russian Academy of Sciences. Six healthy male volunteers, aged 25–35 years, were subjected to 21 days of strict bed rest with a tilt angle of –6°. A needle biopsy of the m.soleus was performed using the Bergström method before the start of HDT BR and on day 21 of HDT BR. The biopsy material was immediately frozen in liquid nitrogen for further Western blot and PCR analysis. Examination of mTORC1 substrates showed a significant decrease in p70 and 4EBP1 phosphorylation after HDT BR. We also observed a significant decrease in the phosphorylation of another ribosomal kinase, p90RSK, a significant increase in eEF2 phosphorylation and an increase in eEF2k mRNA expression. In addition, the phosphorylation of AMPK and its substrate ACC decreased after HDT BR. The data obtained in this work support the hypothesis that a decrease in protein synthesis, together with an increase in proteolysis, contributes to the development of human m. soleus atrophy after 21 days of HDT BR.

Previously, the possibility of increasing the body's resistance to stress with small doses of L-thyroxine was shown. It has not been established whether this effect is related to the action of L-thyroxine itself or is mediated by its activation/potentiation of the effects of other hormones. The aim of the work is to study the role of adrenal hormones in the realization of the protective effect of low doses of L-thyroxine under stress. The work was performed on white mongrel male rats. Stress was modeled by a «time deficit» situation. L-thyroxine was administered in small, close to physiological doses according to the following scheme: the first week – 1.5 μg/kg, the second week – 2.0 μg/kg, the third week – 2.5 μg/kg, the fourth week – 3.0 μg/kg. It was found that stress exposure increases the concentration of iodine-containing thyroid hormones (ITH) in the blood by 23–44%, corticosteroids by 40%, the relative mass (RM) of the adrenal glands by 31%; reduces the RM of the thymus and spleen by 26 and 14%, the level of insulin by 46%; causes damage to the gastric mucosa (GM) with the damage index (DI) is 1.36; increases physical endurance, motor activity and anxiety of animals, reducing the intensity of research reactions. Bilateral adrenalectomy (BA) prevents the activation of thyroid function and eliminates the growth of physical endurance, changes the structure of behavior, determines more significant damage to the GM (DI is 2.7), increased anxiety, inhibition of research behavior under stress. BA limits the protective effect of L-thyroxine under stress, which is manifested by lower values of horizontal motor and research activity, higher anxiety in rats and damage to GM (after administration of L-thyroxine DI under stress without BA is 0.12; against BA is 1.19). This corresponds to a lower concentration of ITH in the blood (by 14–4 3%). Consequently, small doses of L-thyroxine have a stress-protective effect. BA limits, but does not completely prevent its implementation. This indicates that adrenal hormones play an important but not decisive role in the formation of the anti-stress effect of L-thyroxine.

The purpose of this study is to find out what effect the maternal methyl-enriched diet (MED) in the perinatal period exerts on cognitive functions in adult offspring of WAG/Rij rats, a genetic model of absence epilepsy with comorbid depression. Cognitive functions (learning and memory) were evaluated in tests of a novel object recognition (NOR) and a conditioning of fear memory (fear conditioning). The experiments were carry out on 6-months old male WAG/Rij rats. The mothers of the experimental group fed MED, and the mothers of the control group fed the control diet. The NOR test was used to assess episodic memory. This test is based on innate exploratory motivation (novelty preference motivation), which is usually reduced in depression. The conditioning of fear memory is the classic Pavlovian defensive conditioned reflex, manifested in the form of freezing reactions in response to negative reinforcement (electrical stimulation of paws). In the NOR test, in rats of the experimental group the recognition index (a measure of episodic memory), as well as the number of entries to the center of the arena (a measure of explorative motivation) were significantly higher compared with corresponding measures in the control group. However, no intergroup differences were found in the manifestation of the conditioned fear memory (% of freezing reactions) to the context and sound signal. The results indicate that the maternal MED improves episodic memory in the NOR test, but does not affect the conditioned fear memory associated with context and sound signal in adult offspring of WAG/Rij rats.

In recent years, the role of astro- and microglial cells and associated neuroinflammation in the pathogenesis of epilepsy has been extensively discussed. These cells can be in different functional states, the extreme A1 and M1 phenotypes producing predominantly pro-inflammatory (promoting epileptogenesis) proteins, and the A2 and M2 phenotypes producing anti-inflammatory (preventing epileptogenesis) proteins. It has been suggested that the use of drugs that can stimulate polarisation from M1 and A1 to M2 and A2 phenotypes may be a successful strategy for the treatment of epilepsy. Such drugs include agonists of peroxisome proliferator-activated receptor nuclear receptors (PPARs). The aim of this study was to investigate changes in the expression of micro- and astroglial proteins involved in the regulation of epileptogenesis in the dorsal hippocampus of rats in the lithium-pilocarpine model of temporal lobe epilepsy (TLE) and to investigate the effect of the PPAR agonist beta/delta cardarine on these processes. Cardarin was administered at the initial stages of epileptogenesis (within 7 days after induction of the TLE model), and two months later (chronic phase of the model) we analysed the expression of genes of interest in the dorsal hippocampus by real-time RT-PCR. The performed study revealed changes in gene expression of astro- and microglial proteins during epileptogenesis, mainly associated with the enhancement of neuroinflammatory processes and weakening of neuroprotective properties of these cells. In TLE rats the expression of genes of markers of astro- (Gfap) and microglia activation (Aif1), pro- (Il1b, Nlrp3) and anti-inflammatory (Il1rn) proteins, markers of the A1 phenotype of astrocytes (Lcn2, Gbp2) and growth factors (Bdnf, Fgf2) was increased. Gene expression of the protective M2 phenotype Arg1 gene was decreased in TLE rats. The most striking effect of cardarine administration was manifested in the enhanced expression of the marker A2 gene of the S100a10 astrocyte phenotype.

The study examined the role of conscious and unconscious processes depending on the level of arithmetic skill. The participants were divided into two groups according to their arithmetic skill based on the calculation fluency test results. Masked and unmasked single-digit addition problems (primes) followed by correct and incorrect results were presented on the screen. In a conscious perception task (unmasked priming), when large and small problem results were presented, an arithmetic N400 and LPC effects were observed in both groups. In the case of unconscious perception (masked priming), when small problem results were presented, the LPC effect was observed in the group with low arithmetic skill. The fact that the LPC arithmetic effect was discovered during the unconscious presentation may indicate the automatic nature of the encoding and retrieving information processes, reflecting neurophysiological characteristics associated with the level of arithmetic skill.