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Vol 111, No 9 (2025)
EXPERIMENTAL ARTICLES
Effect of ozone on the oxygen-transport function of blood and the content of gasotransmitters (nitric oxide and hydrogen sulfide) in rats
Abstract
Ozone therapy is a highly effective method of rehabilitation of the body in various pathologies, the effects of which can be associated with its influence on the mechanisms of oxygen transport in the blood. The aim of this work is to study the effect of ozone in various concentrations on the oxygen-transport function of the blood, the content of 2,3-diphosphoglycerate and adenosine triphosphate, the gasotransmitter system (nitrogen monoxide and hydrogen sulfide) in rats. The experiment was performed on white outbred male rats (n = 56), which were divided into 4 groups: the control group, which received 1.0 ml of 0.9% NaCl solution intraperitoneally for 10 days, and 3 experimental groups, which were administered 0.9% NaCl solution with an ozone concentration of 1, 10 and 100 μg/kg of animal weight, respectively, for 10 days. Blood oxygen-transport function indices, 2,3-diphosphoglycerate and adenosine triphosphate, nitrate/nitrite and hydrogen sulfide content were determined. Animals that received ozone at a concentration of 10 μg/kg showed an increase in PO2, SO2, P50real, 2,3-diphosphoglycerate, adenosine triphosphate and gas transmitters (nitrogen monoxide and hydrogen sulfide) compared to the control. No changes in blood oxygen-binding properties were observed when using ozone at minimum and maximum concentrations. The revealed effect of ozone (at a dose of 10 μg/kg) on rat blood oxygen-transport function, manifested in a decrease in hemoglobin affinity for oxygen, is realized through an increase in gas transmitters (nitrogen monoxide and hydrogen sulfide), promoting the growth of such modulators as 2,3-diphosphoglycerate and adenosine triphosphate.
Russian Journal of Physiology. 2025;111(9):1441-1452
1441-1452
Separate and combined effects of chronic sleep deprivation and high-fat diet on metabolic parameters and neurobehavioral functions in rats
Abstract
Among the negative consequences of chronic lack of sleep, obesity and its associated metabolic and neurobehavioral disorders occupy a significant position. Chronic lack of sleep leads to increased appetite and a preference for high-calorie foods, thereby provoking a higher risk of developing obesity. The cause-effect relations between short sleep duration and the pathophysiology of obesity, as well as the effects of their combined impact on the organism, remain poorly studied. The aim of this study was to compare the effects of sleep restriction (SR) and high-fat diet (HFD)-induced obesity, both separately and combined, on metabolic parameters and neurobehavioral functions in rats. In the study a model of chronic SR (3 hours of sleep deprivation on a moving platform and 1 hour of rest daily for 5 days) and HFD feeding (8 weeks) was used in male Wistar rats. Control animals received standard dry feed. It has been established that SR leads to an increase in body weight and adipose tissue and impaired glucose tolerance, and with the combination of SR and HFD, the spectrum of metabolic and hormonal disorders expands, including decreased insulin sensitivity, as indicated by an increase in insulin levels and the insulin resistance index. We have demonstrated for the first time that when SR is combined with HFD, neurocognitive indicators, in particular working memory, are also impaired, as evidenced by a decrease in spontaneous alternation in the Y-shaped maze test, while in groups with only SR or HFD, these indicators did not change. It was found that impaired working memory in the SR+HFD group may be associated with dysregulation of the dopaminergic system in the prefrontal cortex. The combined effects of SR and HFD may be considered as a significant risk factor for the development of metabolic disorders and cognitive deficits.
Russian Journal of Physiology. 2025;111(9):1453-1471
1453-1471
The upper extremity’s postural synergies, ensuring the motor task realization of keeping the balanced position of the object in the hand
Abstract
The article presents an analysis of postural and muscular synergies involved in the implementation of motor tasks to maintain the balanced position of an object in the hand while walking. During movement, electromyograms of the superficial muscles of the upper extremities were recorded and video recordings of body segment movements were performed. Synergy parameters were extracted from the recorded signals using factor analysis and the principal component methods. The assumption about the orientation of muscle synergies to stabilize the trajectories of the upper limb segments, which are important for the successful implementation of a motor task, was tested. A general postural synergy has been established that is used for various motor tasks, as well as higher-order synergies that fine-tune posture during movement. Four muscle synergies involved in controlling the movements of the upper extremity have been identified, two of which are the main ones. They are associated with compensation for balance disorders caused by the moments of placing the foot on the support, active extension of the lower limb in the knee and ankle joints. The spatial organization of muscle synergies shows individual strategies for using muscles in their structure, despite the fact that the same moments act as disturbing factors acting on the stabilizing system. Muscle synergies are activated at the moments of the greatest disturbing effect on postural stability and are aimed at stabilizing articular angles and trajectories of movements of the segments of the upper extremity.
Russian Journal of Physiology. 2025;111(9):1472-1488
1472-1488
Response of endoneurium-resident macrophages and neutrophils to sciatic nerve injury and mesenchymal cell transplantation in rats
Abstract
The aim of this work was to study the distribution of resident macrophages and neutrophils in the endoneurium of the rat sciatic nerve early after injury and subperineural administration of MSCs. To clarify the reaction of these cells to peripheral nerve injury, an experimental model of rat sciatic nerve injury was used by ligation (for 40 s) using cell therapy. To identify endoneurium macrophages, an immunohistochemical reaction to the calcium-binding protein Iba-1, a marker of mononuclear phagocytes, was used. Neutrophils were examined on preparations stained with hematoxylin and eosin and toluidine blue. It was found that activation of resident macrophages in the endoneurium of the rat sciatic nerve occurs as early as 1 hour after injury, several hours earlier than neutrophils migrate from the blood vessels to the endoneurium. This indicates that resident macrophages are the first to respond to damage and contribute to the development of Wallerian degeneration processes. It is shown that the use of subperineural transplantation of MSCs leads to a decrease in the activation of resident macrophages and migration of neutrophils. Possible reasons for the established facts are discussed.
Russian Journal of Physiology. 2025;111(9):1489-1500
1489-1500
Hypoxic preconditioning reduces ceramide formation, TNFα levels, and TNFR1 expression in the rat brain in acute cerebral ischemia
Abstract
To study changes in the concentration of ceramide, the main enzymes involved in its biosynthesis, as well as TNFα and TNFR1 expression in the rat brain in acute cerebral ischemia (ACI) and hypoxic preconditioning (HP); to evaluate the relationship of these factors with animal survival and neurological deficit. Experiments were performed on 37 male white nonlinear rats weighing 180–230 g. ACI was modeled by irreversible ligation of the left common carotid artery with simultaneous reversible ligation of the right common carotid artery. The animals were divided into 3 groups: Group 1 – sham operated, Group 2 – rats with ACI, Group 3 – animals with ACI and HP. On the 3rd day of monitoring, neurologic deficit was assessed using the Garcia scale; changes in TNFα and TNFR1, ceramide, serinpalmitoyltransferase, ceramide synthase, acidic and neutral sphingomyelinases were evaluated using immunofluorescence microscopy. ACI led to increased production of ceramide in the brain with elevated levels of all enzymes studied, and was also accompanied by higher levels of TNFα and expression of its receptor TNFR1. HP contributed to the reduction of these effects: the levels of ceramide and sphingomyelinases, TNFα and TNFR1 were suppressed, the neurological deficit became less severe, and the survival of animals was improved in comparison with ACI. HP has shown its effectiveness as a method to reduce the severity of neurological disorders and increase the survival of experimental animals, to prevent changes in proinflammatory factors and ceramide level by the decrease of the main enzymes of its synthesis.
Russian Journal of Physiology. 2025;111(9):1501-1511
1501-1511
Response Characteristics to Pentylenetetrazol Administration in Rats with the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy
Abstract
Epilepsy is a severe neurological disorder, with approximately 30% of patients being therapy-resistant. The lithium-pilocarpine model of temporal lobe epilepsy (TLE) in rats reproduces key features of the disease, but long-term monitoring of spontaneous seizures is labor-intensive, necessitating the search for additional biomarkers of epileptogenesis. In clinical practice, EEG–particularly the analysis of interictal epileptiform patterns – plays a crucial role in epilepsy diagnosis. Provocative tests (sleep deprivation, photic stimulation, etc.) enhance the detection of pathological patterns. In experimental settings, a similar effect can be achieved using low doses of convulsants, such as pentylenetetrazol (PTZ), though such methods are rarely employed. The aim of this study was to investigate the effect of low-dose PTZ on epileptiform activity in the lithium-pilocarpine TLE model in rats and compare this method with maximal electroshock (MES) testing. The TLE model was induced in male Wistar rats (experimental group: pilocarpine after LiCl; control group: saline). Six months later, after the development of spontaneous recurrent seizures, EEG electrodes were implanted on the skull surface. EEG recordings were performed in two stages: baseline and after PTZ administration (40 mg/kg). Three weeks later, seizure susceptibility was assessed using MES. The results showed that baseline EEG recordings revealed no differences between the groups. However, after PTZ administration, a clear distinction was observed: Control rats exhibited regular bursts of high-amplitude sharp waves (4–8 Hz). Epileptic model rats predominantly displayed interictal spikes and spike-wave complexes. In contrast, MES testing showed no differences in threshold currents required to induce hindlimb extension between control and experimental rats. Thus, the provocative test using low-dose PTZ is a highly sensitive method for detecting epileptiform activity in the TLE model, surpassing MES in informativeness. These findings support the potential of this approach for preclinical research.
Russian Journal of Physiology. 2025;111(9):1512-1525
1512-1525
Features of length-dependent changes in calcium transients in the ventricular myocardium in rats of different ages
Abstract
The problem of cardiovascular regulation during aging has received insufficient attention, despite its high social significance. The common pathogenesis of cardiovascular regulation disorders in experimental animals and in elderly people makes it relevant to study the mechanisms of myocardial contractility regulation in a comparative experiment on laboratory animals of different ages. In order to establish the features of length-dependent mechanisms of healthy myocardial contractility regulation during aging, length-dependent changes in the characteristics of force, electrical activity and changes in the intracellular concentration of calcium ions (calcium transient or CaT) in the myocardium of the right ventricle of groups of young (1 month) and old (2.5 years) rats were assessed. The experiments were carried out on the trabeculae of the right ventricle of the hearts of male Wistar rats. In the isometric contraction mode, with varying degrees of stretching, the indices of mechanical tension, CaT and transmembrane action potentials (AP) were recorded. It has been experimentally established that old animal has a smaller amplitude of isometric tension, a lower rate of development of isometric tension, and a longer AP in comparison with young animals. For the first time, age-related features of length-dependent changes in the CaT curves obtained at different preloads of the ventricular myocardium, with their superposition, have been established. In old animals, the duration of the CaT decline by 30% of its amplitude is significantly greater than in young animals. The effect of the degree of acto-myosin overlap on the intracellular kinetics of calcium ions in the ventricular myocardium strips of rats of different ages has been shown, using the developed method of the difference of the curves of calcium transients. The relative amplitude and area of segment III of the CaT difference curves are significantly greater in young animals, in comparison with old ones.
Russian Journal of Physiology. 2025;111(9):1526-1544
1526-1544
Short-term perinatal hypoxia does not affect the functioning of skeletal muscle arteries in adult rats
Abstract
Perinatal hypoxia is one of the most common pathologies in early ontogenesis, which can have a programming effect on the functioning of the vascular system. The latter has been shown for the pulmonary arteries, as well as in several studies on systemic arteries. However, there are no data on the delayed effect of perinatal hypoxia on the functioning of the hemodynamically important vascular region of skeletal muscles. In this regard, the aim of this work was to study the delayed effects of a short-term normobaric hypoxia in early ontogenesis on the functioning of skeletal muscle arteries in adulthood. In this work, normobaric hypoxia (8% O2) was applied for 2 hours in 2-day-old male rats, after which they were raised to adulthood (11-12 weeks) and the functional activity of the sural arteries and the level of systolic blood pressure were assessed. Contractile responses of the sural arteries to an α1-adrenoceptor agonist, endothelium-dependent relaxation responses of arteries to acetylcholine and endothelium-independent relaxation responses to an NO-donor did not differ between the Hypoxia and Control groups. The anticontractile effects of NO and Ca2+-activated potassium channels of large conductance, as well as the procontractile effect of Rho-kinase in arteries were not changed in rats that underwent perinatal hypoxia. Systolic blood pressure levels did not differ between the groups. Thus, according to the results presented in this work, short-term normobaric perinatal hypoxia does not lead to delayed changes in the regulation of sural artery tone and blood pressure in rats in adulthood.
Russian Journal of Physiology. 2025;111(9):1545-1557
1545-1557
Regulation of intracellular calcium during high-frequency rhythmic stimulation of the motor nerve ending of a frog
Abstract
Under physiological conditions, chemical synapses, including neuromuscular junctions, operate rhythmically at different frequencies depending on the functional type of muscle and the state of synaptic contact. Calcium ions (Ca2+) entering the axoplasm through voltage-gated Ca2+ channels during each action potential activate exocytosis of synaptic vesicles and play a key role in modulating the secretory process. The endoplasmic reticulum (ER), which can release Ca2+ ions via Ca2+-dependent release, may contribute significantly to intracellular Ca2+ dynamics. Optical recording techniques using Ca2+-sensitive fluorescent dyes are used to monitor changes in intracellular Ca2+. However, such an evaluation must pay special attention to the dye's binding characteristics with Ca²⁺ ions, specifically its affinity, because the degree of dye saturation affects the parameters of the Ca²⁺ response being investigated. In this study, the low-affinity dye Magnesium Green was used to analyze changes in the intracellular Ca2+ ions concentration in the neuromuscular synapse m. cutaneus pectoris of the frog during rhythmic stimulation, which allows correct assessment of Ca2+ signals. With increasing frequency of motor nerve stimulation, the smooth increase at 20 Hz of Ca2+ response was replaced by a biphasic increase at 50 Hz and a sharp increase at 70 Hz. This indicates the inclusion of additional Ca2+ sources, which may be the ER. Blocking ryanodine and inositol receptors abolished the increase in Ca2+ response at higher frequencies of nerve stimulation. Blocking Ca2+ ATPases ER (SERCA) resulted in a dramatic increase in the Ca2+ response and eliminated its multiphasic character. It is shown that the change in Ca2+ transient reflects the accumulation of intracellular Ca2+ in the axoplasm and depends on the activity of SERCA, ryanodine and inositol receptors. The use of a low affinity fluorescent Ca2+ dye makes it possible to track the contribution of these systems to the formation of the intracellular concentration of the main ions that determine the process of neurosecretion.
Russian Journal of Physiology. 2025;111(9):1558-1575
1558-1575
Articles
1576-1578