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Vol 111, No 3 (2025)

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REVIEW

Hormonal modulation of NK-cell plasticity during pregnancy

Shirshev S.V.

Abstract

The article presents a review of scientific studies on the effect of hormones produced by the placenta during physiological pregnancy on plasticity of NK cells, accompanied by a change in the phenotype and functional activity of the latter. Analysis of scientific studies has shown the primary role of estrogens, progesterone, human chorionic gonadotropin, leptin, ghrelin and kisspeptin in the induction of NK cell plasticity processes. Hormones are able to transform NK lymphocytes of peripheral blood into decidual (d)NK cells with reduced cytotoxicity, expression of inhibitory receptors and increased production of the fetoprotective cytokine TGF-b. At the same time, hormones reduce the production of such abortogenic cytokines as IL-17A and IFN-γ. The action of hormones is carried out in concentrations characteristic of pregnancy and is specific. In addition, hormones can recruit other cells of the placental microenvironment. In addition, hormones support the phenomenon of plasticity, exerting a similar effect on dNK cells, which apparently enhances the processes of immune tolerance towards the fetus and promotes its physiological development during pregnancy.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):379-406
pages 379-406 views

A meta-analysis study of melatonin effect on the behavior of rats kept under standard conditions

Kuzmenko N.V., Tsyrlin V.A., Pliss М.G., Galagudza М.М.

Abstract

It is known that the pineal gland hormone melatonin, synthesized during hours of darkness, regulates daily and seasonal changes in metabolism, reproduction and behavior. To date, many experimental studies have been conducted investigating the effects of exogenous melatonin administration on behavior in various tests in rats. The aim of this work is to use meta-analysis to investigate melatonin effects on the behavior of rats kept under standard conditions. We selected 57 publications for meta-analysis that studied melatonin monotherapy: 35 papers with the open field (OF) test, 23 papers with the elevated plus maze (EPM), 12 publications with the forced swim (FS) test, and 21 papers with the Morris pool (MP). The meta-analysis showed that a single peripheral administration of melatonin in low doses (≤ 1 mg/kg/day) increases the locomotor activity of rats in the OF test. Long-term administration of melatonin also contributed to an increase in the locomotor activity of rats. Melatonin has an anxiolytic effect, which is confirmed by an increase in the time spent by rats in the center of the OF test and in the open arms of EPM. A reduction in the immobilization period in the FS test indicates an antidepressant effect of the hormone. The anxiolytic and antidepressant effects were more pronounced in females than in males. No convincing evidence of a dose effect on the anxiolytic and antidepressant effects of melatonin was obtained. With melatonin therapy, there was a tendency to increase the time for rats to search for a platform in MP. In most studies, the hormone was administered intraperitoneally, and researchers usually used young animals. For these reasons, we were unable to correctly assess dependence of melatonin effects on the route of administration and the age of rats.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):407-435
pages 407-435 views

EXPERIMENTAL ARTICLES

T-system remodeling of rat cardiomyocytes in metabolic syndrome

Stepanov A.V., Filippov Y.A., Pestryakova L.I., Karnishkina O.Y., Panov A.A., Dobretsov M.G.

Abstract

Heart failure of various etiologies, including diabetic cardiomyopathy (DCM), is a worldwide problem. However, the features of DCM pathogenesis, including the role of t-tubules in this process, are not fully understood. Available literature data on T-system remodeling in diabetes models are sometimes contradictory, and t-tubule changes in some of them have been shown already at the prediabetes stage. So, the aim of this work was to evaluate changes in the t-tubule system in a model of metabolic syndrome (MS), preceding the development of type II diabetes mellitus, in rats on high-carbohydrate and high-carbohydrate and high-fat diets. The experiments were performed on male Wistar rats. MS induction in the animals of the experimental groups was carried out using high-carbohydrate (HC) and combined high-carbohydrate and high-fat (HCHF) diets for 10 weeks. The weight of the animals, of the abdominal fat, and of the heart were also assessed, and a glucose tolerance test (GTT) was also performed. The structure of the T-system was studied using confocal microscopy on isolated hearts stained with DI-8-ANEPPS. Rats on the HCHF diet developed more severe MS: body weight, abdominal fat mass, and fasting blood glucose level were significantly higher in these animals than in the controls. Signs of glucose tolerance in the GTT were also revealed. Rats on the HC diet were characterized by the development of moderate MS, manifested only in an increase in abdominal fat mass. Signs of t-tubule system remodeling were also revealed only in the HCHF diet group: they were manifested by a reliable increase in the average interval between t-tubule rows. This differs from the results obtained in the model of type I diabetes and prediabetes. Thus, it can be concluded that changes in the T-system in rat cardiomyocytes appear already at the stage of MS induced by the HCHF diet and are similar to the changes described for type II diabetes, but differ from the changes in type I diabetes and prediabetes, which may indicate different pathogenesis pathways of DCM in different types of diabetes.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):436-446
pages 436-446 views

Postural stability in female rhythmic and artistic gymnastics athletes: the role of visual and somatosensory signals

Niazi E.S., Samigullin B.R., Baltin M.E., Fedyanin A.O., Baltina T.V., Botova L.N., Zverev A.A.

Abstract

The study was devoted to the assessment of postural stability in female athletes involved in rhythmic (n = 17), artistic (n = 20) gymnastics and non-athletes (n = 19). The main objective was to identify the features of the center of pressure (CoP) oscillations in female and non-athletes under various conditions of activation of visual and somatosensory inputs. The method of computer stabilometry was used on the automated complex “Stabilan-01-5”. To assess postural stability, the parameters of the stabilographic test were analyzed: linear velocity of CoP movement (ALV, mm/sec), angular velocity of CoP movement (AAV, deg/sec) and ellipse area (EIIS, sq. mm), the Romberg coefficient was calculated. Spectral analysis of stabilographic signals was conducted. The participants performed tests in a normal stance on a hard and soft surface with their eyes closed and open.

The results showed that CoP oscillations in female and non-gymnasts in a calm stance were comparable, but differences were observed on a soft surface. Rhythmic and artistic gymnasts demonstrated better postural stability indicators, which is explained by their ability to integrate proprioceptive and visual signals. Spectral analysis showed smaller fluctuations in the high-frequency range in both rhythmic and artistic gymnasts, which indicates the formation of specific motor and neuromuscular strategies in them. It was also found that rhythmic gymnasts were more dependent on visual control to maintain postural stability, which is probably due to the need to accurately assess the distance and body position when performing elements specific to this sport. The results obtained can serve as a basis for developing individual training programs taking into account sensory integration and movement control in different groups of athletes.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):447-462
pages 447-462 views

Comparative analysis of changes in heart rate parameters of female and fetal rats under conditions of hemic hypoxia

Vdovichenko N.D.

Abstract

We performed a comparative analysis of changes in the cardiac activity parameters under conditions of hemic hypoxia created by the introduction of sodium nitrite in female rats and their fetuses on gestation days 18 (E18) and 20 (E20). In the last trimester of prenatal development, under the conditions of the hemic hypoxia model, an increase in the sensitivity of the female organism to oxygen deficiency is observed at E20 compared to E18. Conversely, an analysis of the physiological indices of the fetuses revealed a greater resistance of the fetal cardiovascular system to hypoxia on E20 than on E18. Analysis of heart rate variability (HRV) showed the active participation of the catecholaminergic system in the emergency mobilization of energy and metabolic resources in fetuses.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):463-474
pages 463-474 views

The effect of mechano-activated channels on passive stiffness and contraction amplitude of slow muscle

Sergeeva K.V., Tyganov S.A., Zaripova K.A., Shenkman B.S.

Abstract

Recently, highly specialized mechano-activated (MA) channels of the Piezo family have aroused increased interest among researchers in connection with their participation in the processes of mechanotransduction in mammals. However, until now nothing has been known about the role of these channels in the regulation of muscles’ passive stiffness and contraction. We assumed that both passive deformation of an isolated muscle and induced twitch and tetanic muscle contraction would lead to activation of Piezo1 channels, which increases passive stiffness and amplitude of muscle contraction. The purpose of the study: using Dooku1, a specific inhibitor of Piezo1 channels, and gadolinium chloride, a non-specific inhibitor of MA channels, to evaluate the possible contribution of Piezo1 channels to the mechanical response of an isolated slow muscle to passive deformation and induced twitch and tetanic contractions. The experimental results showed that the use of gadolinium led to a significant decrease in the parameters of passive muscle stiffness. Interestingly, the specific blocking of the Piezo1 MA channels using Dooku1 did not affect these parameters. At the same time, when the isolated muscle was treated with Dooku1 solution, the maximum tension of the induced twitch and tetanic contractions decreased by 21 and 25% respectively. Also, incubation of muscles in Gd3+ solution did not lead to significant changes in the parameters of induced contraction. Thus, we have shown that the MA channels, which can be blocked by Gd3+, are stimulated by passive muscle stretching and are involved in the regulation of muscle stiffness. At the same time, the Piezo1 MA channels are activated during muscle contraction and are involved in its regulation. It can be assumed that the participation of calcium channels in maintaining muscle stiffness and in the realization of muscle contraction can be carried out by additional activation of myofibrils with calcium ions, the concentration of which in muscle fiber increases as a result of the activity of these channels.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):475-483
pages 475-483 views

Age-related changes in spreading depolarization during generalized epileptiform activity induced by flurothyl

Zakirova G.F., Chernova К.A., Vinokurova D.E., Khazipov R.N., Zakharov А.V.

Abstract

Spreading depolarizations (SDs) often accompany epileptiform discharges and participate in their termination. However, the factors that determine the occurrence of SD during epileptic seizures remain poorly understood. In this study, we investigated the influence of age on this phenomenon by performing multichannel intracortical recordings of electrical signals at different depths of the somatosensory cortex in rats during generalized epileptic discharges induced by flurothyl inhalation. We found that in juvenile rats (1–2 months old), SD frequently accompanied flurothyl-induced seizures, occurring in almost half of the cases. In contrast, SD events were much less frequent in immature rats (less than 3 weeks old) and adult rats (older than 3 months). In all age groups, SD originated in the superficial cortical layers and propagated downward into deeper layers. However, the depth of SD penetration was also age dependent: SDs spread deeper in juvenile rats compared to immature and adult animals. Thus, the propensity for SD during flurothyl-induced seizures follows a bell-shaped age profile, with the highest frequency and deepest propagation observed in juvenile animals. These findings underscore age as a critical determinant of the occurrence and characteristics of SD during epileptiform activity in the cortex.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):484-495
pages 484-495 views

The effectiveness of hypercapnic-hypoxic training to increase resistance to acute hypoxia in rats with LPS-induced endotoxemia

Donina Z.A.

Abstract

Severe sepsis (endotoxicosis), similar to cytokine storm, is aggravated by acute respiratory failure, hypotension, hypoxemia and hypercapnia, which is the main cause of high mortality. The aim of the work is to study the effectiveness of hypercapnic-hypoxic training for the relief of cardiorespiratory disorders and increased tolerance to acute hypoxia in rats with LPS-induced endotoxicosis. The experiments were conducted on anesthetized male Wistar rats. Endotoxicosis was simulated by administration of LPS (Escherchia coli) 7 mg/kg. The assessment of resistance to hypoxia was carried out by the rebreathing method (RM) with a gradual decrease in oxygen in the rebreather from 21% to the onset of apnea. 3 groups of animals were studied: I – control – NaCl, II – LPS, III – LPS+HHT. The following parameters were recorded: external respiration, mean blood pressure (APm.), saturation (SpO2), fraction of inhaled O2 (FiO2) and CO2 (FiCO2), time of onset of apnea, the amount of spontaneous respiratory recovery (autoresuscitation) in the posthypoxic period. The LPS+HHT group was previously subjected to hypercapnic-hypoxic training. For this purpose, the rebreather was filled with room air, the volume of which was selected in such a way that during the breathing of the animal into / out of the rebreather, FiO2 decreased to 11 ± 0.5% for 3 minutes, and FiCO2 increased to 5.0 ± 0.5%, after which the rat was switched to breathing air. The training regime consisted of 3 cycles: 3 min – HHT, 5 min – normoxia. It was found that the maximum decrease in resistance to acute hypoxia was observed in rats with LPS, respiratory recovery after apnea was carried out in 10%, HHT prevented a fatal decrease in SpO2 and APm, autoresuscitation occurred in 100% of cases. Based on the data obtained, it can be concluded that the combined effects of hypercapnia and hypoxia effectively contribute to increased tolerance to acute hypoxia in rats with LPS-induced endotoxemia.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):496-507
pages 496-507 views

Effect of synthetic and biogenic iron oxide nanoparticles on histopathological parameters of mouse kidneys

Kireeva A.V., Kolenchukova O.A., Biryukova E.A., Stolyar S.V.

Abstract

The unique physical, chemical and magnetic properties of iron oxide nanoparticles (INPs) open up wide prospects for the use of nanomaterials in the diagnosis and therapy of various diseases. Despite the high interest from the scientific community, the mechanism of the effect of INPs on the physiology of living organisms has not been fully investigated. This is due to the fact that the toxicity of nanoparticles depends on many factors, including size, synthesis method and the presence of the shell. The research is aimed to investigate the effect of INPs on the morphological structure of the kidneys, depending on the method of synthesis and the presence of a polysaccharide shell after oral administration. In the study was used ferrihydrite INPs of synthetic and biogenic origin. The experiment was conducted on 3 groups of animals (55 mice): Group 1 – control (15 mice), feed without additives; group 2 (20 mice) – experienced, synthetic INPs were introduced into the feed; Group 3 (20 mice) was an experimental group, encapsulated biogenic INPs were introduced into the feed. The collection of biological kidney material for histological examination was carried out on the 1st day and on the 22nd, 36th day after the introduction of INPs into the feed. Histological examination was performed using a standard technique. Staining of histological sections was carried out with hematoxylin-eosin and Perls. The studied morphometric parameters of the kidney were analyzed using the Morphology 7.0 program. As a result of the study, it was found that repeated administration of INPs of both synthetic and biogenic origin is accompanied by hemodynamic disorders in the studied organ, as well as dystrophic and necrotic changes in the cells of the renal parenchyma, leading to the development of renal failure. The most pronounced reactivity is possessed by INPs obtained by the biogenic method, which is probably due to the presence of a polysaccharide shell and the crystalline structure of the iron compound.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):508-521
pages 508-521 views

Study of the influence of long-dependent changes in myosin bridge kinetics on calcium transient in the myocardium of the right atrium and right ventricle of rats

Lisin R.V., Balakin A.A., Zudova A.I., Protsenko Y.L.

Abstract

Heterometric regulation of myocardial contractility is the most important property regulating the pumping function of the heart. Calcium ions play a key role in the activation and regulation of muscle contraction. In addition to changes in the degree of actin-myosin filament overlap, one consequence of myocardial stretch is a length-dependent change in the shape and duration of the intracellular calcium transient (CaT). As the degree of myocardial stretch increases, the duration of the CaT decreases in the upper half of the CaT decline and increases in the lower half. To determine the contribution of myosin bridge kinetics to CaT changes, length-dependent changes in CaT were assessed in three states of myosin bridge kinetics; (1) intact, (2) slowed under the influence of omecamtiv mecarbil 1 µM (OM), and (3) blocked under the influence of blebbistatin 10 µM (BB). It was found that length-dependent multidirectional changes in CaT decay (CaT crossover phenomenon) were pronounced in the right ventricular (RV) myocardium and weak in the right atrial (RA) myocardium of intact male nine-week-old Wistar rats. OM significantly slows the rate of tension development and decline in myocardium of RA and RV rats; enhances length-dependent changes in CaT duration; OM decreases the duration of CaT at 80% of its amplitude and increases the duration of CaT at 20% of its amplitude in both RA and RV. BB almost completely abolishes the ability of the myocardium to develop tension; length-dependent changes in CaT duration are monotonous, CaT crossover in RV myocardium disappears. The phenomenon of CaT crossover in the myocardium of the RV is a consequence of the attachment and detachment of myosin bridges to the thin filament. The absence of length-dependent changes in CaT in rat RA myocardium seems to be associated with a more developed calcium sequestering system in RA, in comparison with the calcium sequestering system in RV.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):522-541
pages 522-541 views

The functional condition of the neuromotor apparatus of the calf muscles in rats during the recovery of motor activity after simulated gravitational unloading

Fedianin A.O., Baltin M.E., Sabirova D.E., Baltina T.V., Iskakov N.G., Eremeev A.A.

Abstract

To reduce the duration of the recovery period after space expeditions, as well as high-quality effective therapy of conditions associated with physical inactivity on Earth, it is necessary to understand the mechanisms of adaptive rearrangements of morphofunctionally different motor systems at all levels of their organization. The aim of the study was to assess the functional condition of the central and peripheral links of the neuromotor apparatus of the rat calf antagonist muscles under conditions of readaptation to the action of the support reaction force and axial loads after simulated gravitational unloading. The study used electromyographic testing methods and also determined the wet and dry weight of the soleus and tibialis anterior muscles. The experimental results showed significant changes in the parameters of reflex and motor responses of the studied muscles. The recorded data indicated a decrease in the reflex excitability of the spinal motor centers on the 1st day of the readaptation period and its increase at the following stages: on the 3rd day for the soleus muscle, on the 7th day for the tibialis anterior. Significant transformations of the functional condition and peripheral parts of the motor systems were also observed, as well as a gradual recovery of muscle weight. More pronounced changes and a longer recovery period were recorded during testing of the slow posterotonic soleus muscle. The information obtained can be useful for developing new and improving existing strategies for motor rehabilitation.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2025;111(3):542-556
pages 542-556 views