Vol 110, No 10 (2024)

This abstract discusses the oligomerization of G protein-coupled receptors (GPCRs), which significantly expands the functional capabilities of cells in living organisms by modulating intracellular signaling pathways. This provides a variety of physiological effects in both normal and pathological states. The structure and localization in the brain of one of the most studied heterodimers, the D1-D2 receptor complex, and its signaling cascades, which correlate with the development of depressive disorders, are examined. Sexual differences in the functioning of this heterodimer are analyzed, and the issue of the selectivity of bivalent synthetic ligands in activating specific intracellular pathways is discussed, highlighting their potential as therapeutic targets for the targeted treatment of depressive disorders. The concluding part of the abstract addresses the diversity of dopamine receptor heterodimers with other members of the GPCR family and their role in the pathophysiology of depression.

Since the last century it has been known that inert gases can cause a range of physiological effects. The biological activity of inert gases is an extremely multifaceted phenomenon. Despite the similarity of most physical and chemical characteristics, they are able to affect many organs and tissues by interacting with a variety of protein targets. Currently, it is known that xenon, krypton and argon are capable of changing the functional state of the central nervous system and correcting some psychoemotional disorders. In addition, they influence the processes of apoptosis and cellular response to stress. Noble gases affect the state of the immune system and various parameters of homeostasis. The cytoprotective effects of helium on the cardiovascular and respiratory systems have also been convincingly demonstrated. Thus, noble gases are currently being considered as potential means of correcting various diseases.

This review is devoted to the analysis of literature data on the physiological effects of noble gases identified in biomedical studies on patients, as well as in cell culture and in vivo models. Each chapter of the review is devoted to a particular gas of this group, starting with the most studied ones. For each of the noble gases (helium, neon, argon, krypton, xenon and radon) their physiological activity, the possibility of using these substances in medicine and some known mechanisms of their action are considered. Moreover, in the review existing data were critically analyzed and key gaps that need to be filled in future research were identified.

Risk factors associated with environmental exposure, especially during critical periods of intrauterine development, affect fetal development and increase the risk of certain diseases in adulthood including cardiovascular diseases (CVD). Hypoxia is considered the most common and clinically significant form of intrauterine stress that causes systemic pathological changes, in 78% of cases associated with cardiovascular system disorders. The purpose of this study was to evaluate the effects of acute hypoxia on the 10th day of gestation on heart rate and its regulation in rats’ offspring of prepubescent and pubertal age, as well as to analyze the dependence of resulting disorders on gender.

By the beginning of puberty the heart rate of rats survived prenatal hypoxia was significantly higher than in control accompanied by significant decrease in heart rate variability (dX) which naturally leads to stress index (SI) increase indicating growing sympathetic activity in heart rhythm regulation. At the same time the base heart rate in animals suffered intrauterine hypoxia turned out to be lower than in control. The fact that matured animals of both sexes, survived intrauterine hypoxia in early organogenesis, also show changes in dX and SI indicates long-term and irreversible disorders in heart rhythm regulation. Thus hypoxia during early organogenesis is of a programming nature potentially increasing the risk of developing CVD in adult animals. Moreover the autonomic system balance shift towards the activation of sympathetic tone was more pronounced in females making them more vulnerable to the risk of developing cardiac pathology in puberty.

Molecular hydrogen demonstrates antioxidant and anti-inflammatory properties. It has been shown to have a protective effect in several cardiovascular diseases. The aim of this work was to study the effect of breathing atmospheric air containing 4% hydrogen on the degree of development of monocrotaline-induced pulmonary hypertension and associated lung tissue inflammation, as well as the severity of renovascular hypertension in Wistar rats. Methods. Monocrotaline-induced pulmonary hypertension (MCT-PH) was used as a model of small circle hypertension. Three groups of animals were used in the experiment: "Control" – animals injected with monocrotaline solvent, "MCT-Control" and "MCT-H₂" – groups injected with MCT once. The "Control" and "MCT-Control" groups breathed atmospheric air for 21 days, and the "MCT-H₂" group breathed air containing 4% hydrogen. Inhalations were kept constant until 21 days. On day 21, haemodynamic parameters were measured under urethane anesthesia and lung samples were fixed for subsequent morphological analysis. Renovascular hypertension 1R1С (RVH) was used as a model of systemic hypertension. There were two groups in the experiment: RVH-C – rats breathed atmospheric air and RVH-H₂ rats breathed air containing 4% hydrogen. During the experiment, systolic blood pressure (SBP) was measured and renal excretory function was assessed. On day 28, haemodynamic parameters were measured under urethane anesthesia. Results. In the MCT model, hydrogen had no effect on the haemodynamic symptoms of MCT hypertension, but decreased mean blood pressure (MBP), SBP and the measured markers of connective tissue remodeling in the lungs, TGF-β and MMP-9, and resulted in decreased tryptase secretion and mast cell counts. In the RVG model, hydrogen breathing decreased MBP, SBP and had no effect on renal excretory function. Conclusion. Inhalation of 4% hydrogen reduces systemic MBP and SBP in both models of arterial hypertension, reduces the severity of the inflammatory process, regulates the phenotypic and functional status of mast cells and inhibits the activity of profibrotic factors in lung tissue in MCT-PH. It is likely that the central action of hydrogen is combined with its anti-inflammatory and anti-fibrotic effects.

Aerobic physical training is used to prevent and correct many cardiovascular disorders. To study the effects of such physical exercise, various methods of training are used in rodents, among which voluntary wheel running is of particular interest, because it is close to the natural rat locomotion in terms of the pattern of motor activity and is devoid of stressful influence. The aim of this work was a comprehensive study of the effects of wheel running on the nervous control of heart rate (HR) in rats. At the age of 6 weeks, the animals were divided into two groups: training (TR, free access to wheels, n = 11) and sedentary control (CON, n = 12). After 6 weeks of training, ECG was recorded in freely moving rats using skin electrodes in baseline, after blockade of cardiac nervous influences and under air-jet stress (4 min). The effects of the autonomic nervous system were analyzed by administering a β1-adrenergic blocker and a peripherally acting M-cholinoceptor blocker, and by analyzing cardiac rhythm variability using spectral and wavelet analyses. TR group showed a decrease in the baseline HR level compared to the CON group. The decrease in HR upon administration of atenolol (2 mg/kg) did not differ between the groups, but methylatropine (1 mg/kg) caused a more significant increase in HR in the TR group than in the CON group. With the combined action of atenolol and methylatropine, HR levels did not differ between the groups. The rats of the TR group showed an increase in the contribution of high-frequency (0.75–3 Hz) oscillations to the total spectrum power of the RR interval. During air-jet stress, TR group showed a more pronounced increase in HR compared to the CON group. In addition, in the TR group, a decrease in the amplitude of HR high-frequency oscillations was observed during stress, while in the CON group, such a decrease was absent. Thus, the voluntary wheel running is accompanied in the rat by an increase in parasympathetic influences on the heart, which is manifested in an increase in respiratory sinus arrhythmia and in an increase in vagal influence on the resting HR level. Moderate bradycardia at rest provides the possibility of a more pronounced increase in HR during emotional stress because of the suppression of parasympathetic cardiac influences.

WAG/Rij rats are widely used as a genetic model of absence epilepsy. Approximately 15–50% rats of the strain are susceptible to audiogenic seizures. WAG/Rij rats demonstrate depressive-like behavior. After preliminary sound provocation an increased level of anxiety was found in audiogenic susceptible WAG/Rij subgroup. Electrophysiological and behavioral studies suggest the involvement of the dopaminergic system in both absence and audiogenic epilepsy. An increased binding density to dopamine receptors was found in the dorsal striatum subregions in audiogenic prone rats compared to non-audiogenic. The study aims were (1) to determine whether behavioral changes in WAG/Rij rats were genetically determined or induced by prior sound stimulation; (2) how regions of the dorsal striatum with different density of dopamine receptors in subpopulations of WAG/Rij rats are involved in the absence epilepsy control. The study was conducted using two rat groups: WAG/Rij-nonAGS (absence epilepsy) and WAG/Rij-AGS (mixed epilepsy). The study was performed using tests: “Elevated plus maze”, “Forced swimming” and “Three chamber sociability test”. High-frequency deep brain stimulation was performed for evaluation of dorsal striatum involvement in the absence seizure control. After experiments animals were tested for the susceptibility to audiogenic seizures. It demonstrated that the increased level of anxiety in WAG/Rij-AGS rats is genetically determined, while depressive-like behavior in WAG/Rij rats is not dependent on a predisposition to audiogenic seizures. Deviations in social behavior were observed in WAG/Rij-AGS rats. Stimulation of the dorsal striatum indicates differences in the control of absence and mixed forms of epilepsy in the

Liver diseases accompanied by obstructive cholestasis (OC) often depend on sex. Prolactin hormone levels are often elevated in a variety of hepatopancreatobiliary zone diseases, which is an adverse prognostic sign. To clarify the role of prolactin in the development of pancreatitis under OC conditions, structural changes in hepatic and pancreatic tissue female rats against the background of hyperprolactinemia were investigated. The rats were divided into the following experimental groups: group K – control animals; group HyperPrl – animals with normal hepatic function against the background of hyperprolactinemia; group BP – animals with biliary pancreatitis under OC; group BPhyperPrl – animals with biliary pancreatitis under OC against the background of hyperprolactinemia. Hyperprolactinemia was modeled by transplanting the donor's pituitary gland under the recipient’s kidney capsule. Biliary pancreatitis was simulated with a ligation of the biliopancreatic duct 1 cm prior to its discharge into the duodenum, causing obstruction of the ducts of the splenic segment of pancreas. After 14 days of operations, a biomaterial was collected. The biochemical indicators of the blood serum confirmed the development of ОС and pancreatitis. The structure of the pancreatic parenchyma in the BP and BPhyperPrl groups was changed, especially in the splenic segment. In both groups, tubulo-insula and tubulo-acinar complexes, inflammatory infiltration, acinaro-ductal metaplasia were found, which was accompanied by severe pancreatic parenchyma fibrosis in the group BPhyperPrl. It is important to note that the duodenal segment of pancreas continued to compensate for pancreatitis development in the BP and BPhyperPrl groups. In the hepatic tissue, histological confirmation of the development of obstructive cholestasis was shown in the BP and BPhyperPrl groups, with the loss of the beam structure of hepatocytes and the development of pericellular fibrosis against the background of hyperprolactinemia. Thus, we first showed in our work that female rats with increased prolactin concentration on the background of OC develop a heavier form of pancreatitis with a pronounced pancreatic fibrosis. This model of the development of biliary pancreatitis under OC can be used not only to study the role of prolactin in disruption of the pancreas, but also its participation in compensatory reactions to maintain the work of the exocrine part of the pancreas in this pathology.