


Vol 60, No 4 (2024)
ОБЗОРЫ
Role of apoptosis-associated proteins p53 and bcl-2 in the pathogenesis of nervous system diseases
Abstract
Diseases of the central nervous system occupy a leading place, along with cardiovascular and oncological diseases, and the proportion of patients suffering from diseases of the nervous system is increasing as the population ages. This group of diseases includes acute conditions, such as ischemic stroke, and chronic multifactorial diseases — Alzheimer's and Parkinson's diseases, epilepsy, etc. The development of specific methods for their treatment is difficult, and these drugs are not very effective. Almost all brain diseases are based on common mechanisms such as oxidative stress, inflammation and neuronal death. Most often, cells die by apoptosis due to an imbalance between pro-apoptotic and anti-apoptotic factors. This work examines two of them: the apoptosis-promoting transcription factor and tumor suppressor p53 and its opposing B-cell lymphoma protein Bcl-2. The choice of these proteins for study is due to the fact that both proteins are key regulators of apoptosis and are important in the pathogenesis of nervous diseases, since neurons are not highly proliferating cells. The p53 protein is involved in the regulation of many genes responsible for DNA repair, apoptosis, and other biochemical cellular processes; this is especially important when studying neuronal pathology. Bcl-2 suppresses apoptosis in various cells, including neurons, by controlling mitochondrial membrane permeability and inhibiting caspases. In diseases, its expression can either increase, for example, in the case of malignant tumors, or decrease, as in the case of neurodegenerative processes. It has been established that p53 and Bcl-2 are in close interaction in the process of regulating apoptosis; their ratio may be an important prognostic factor. The purpose of this work was to assess the role of these proteins in the pathogenesis of various diseases of the nervous system, and to search for general patterns of changes in their expression and coexpression.



EXPERIMENTAL ARTICLES
Level of tryptophan signaling molecules in children with different dynamics of obesity development
Abstract
The high incidence of obesity in children is an extremely pressing problem in the modern health care system of many countries. There is an increase in the incidence of obesity in children in Russia, which is dangerous not only due to the development of somatic concomitant pathologies, but also to a violation of the social adaptation of children. Without a doubt, the search for early biochemical indicators of stabilization and progress of obesity in older age is very important for the formation of a risk group and timely prevention of the development of obesity and its complications. Our study showed that when assessing the various dynamics of obesity development, it is necessary to take into account the gender of the child, which is ignored in many cases. A decrease in serum serotonin concentrations may be considered as an indicator associated with the stabilization or progression of obesity in girls. Whereas in boys prone to stabilization and/or progression of obesity, a reduced serum level of indole-3-acrylate may act as a predictor marker.



Comparative Skeletopy of the Mammalians Lumbar Spinal Cord
Abstract
The spinal cord is the most phylogenetically ancient part of the central nervous system. The more rapid growth of the spine in relation to the spinal cord in ontogenesis leads to the fact that in adult mammals some segments of the spinal cord are shifted ro strally in relation to the eponymous vertebrae, which is called ascension of the spinal cord. Based on literature data, we compared the skeletotopy of the lumbar spinal cord of 17 species of mammals. In 4 species, we also compared the skeletotopy of newborn and adult animals. The ratio of the length of the L2 segment to the length of the VL2 vertebra and the number of the vertebra in which the 29th segment of the spinal cord is located, characterizing the degree of ascension, were determined. Based on literature data, we determined characteristics frequently used in comparative studies: finger dexterity and encephalization coefficient. It has been shown that different species differ to a greater extent in the relative length of the rostral lumbar segments, and within the same species, newborns differ from adults in the relative length of the caudal lumbar segments. For most species, the degree of spinal cord ascension significantly positively correlates with finger dexterity and the encephalization coefficient. The considered macroanatomical characteristics of the spinal cord may be used to analyze the relationships between adaptive mechanisms in various mammalian species.



The Effects of Phenanthrene on Electrical Activity in Ventricular Cardiomyocytes of Atlantic Cod (Gadus morhua)
Abstract
The production of oil on the Arctic shelf and its transport along the Northern Sea Route increase risks of pollution of the ecosystems in the Arctic seas with oil and oil products. Today, polyaromatic hydrocarbons are known as the most toxic oil components, and phenanthrene is predominant in terms of its concentration in oil and physiological effects. Phenanthrene affects the electrical activity of fish heart, but its effects are species-specific. At the same time, the effects of phenanthrene on cardiac function in Arctic fishes, including economically important commercial species, are studied not enough. This study examines the effects of phenanthrene on electrical activity and ionic currents in ventricular myocardium of Atlantic cod (Gadus morhua). The major ionic currents in cod myocardium were IKr, IK1, INa and ICa. Phenanthrene (1 μM) did not affect the duration of action potentials (APs) recorded in isolated cod ventricular cardiomyocytes using patch clamp method. Meanwhile, phenanthrene suppressed rapid delayed rectifier current IKr by 61.33 ± 3.94%, decreasing the repolarization reserve of the myocardium. Phenanthrene did not affect nor the level of resting membrane potential, not background inward rectifier current IK1. Also, application of phenanthrene decreased AP upstroke velocity in cod myocytes, which was due to the suppression of fast sodium current INa. Finally, phenanthrene slightly reduced the amplitude of calcium current ICa and accelerated its inactivation, which overall led to the decrease in ICa charge transfer. Thus, the effects of phenanthrene on cod myocardium at cellular level can be described as potentially proarrhythmic, which makes the populations of cod in Arctic seas vulnerable to pollution of the aquatic environment by oil components after oil spills due to technological disasters.



Immunofluorescent Localization of Ca²⁺-Sensor Proteins in The Somatic Motor Muscles of The Earthworm Lumbricus terrestris
Abstract
The method of immunofluorescent staining of earthworm somatic muscle samples showed the presence of calmodulin, Ca²⁺-calmodulin-dependent protein kinases type 1 and type 2, synaptotagmin type 2 and type 7 and calcineurin A. These proteins are detected in both synaptic and extrasynaptic regions of the motor muscle. However, for synaptotagmin type 2 and type 7, calcineurin A, their predominant localization in the area of neuromuscular synapses has been established. Besides, synaptic localization for synaptotagmin 7 and calcineurin A is most clearly expressed.



Influence of apamin on the extracellularly recorded action potentials profiles of subepicardial cardiomyocytes of the rat heart in myocardial infarction
Abstract
The role of small-conductance Ca²⁺-activated K⁺-channels (SK channels) in the pathogenesis of cardiomyopathies of various etiologies remains poorly understood. The purpose of this work was to evaluate the effect of the blocker of SK channels, apamin, on the extracellularly recorded action potentials (eAPs) of subepicardial myocytes in the left ventricles of sham-operated rats and rats with myocardial infarction caused by ischemia-reperfusion. It was found that local delivery of the SK channel blocker apamin at a concentration of 500 nM to the eAP recording area did not affect the eAP profiles in the group of sham-operated rats but caused a significant slowdown in the repolarization time and a decrease in the afterhyperpolarization phase of eAPs in the group of rats with myocardial infarction. These data suggest that changes in the waveform of eAPs after infarction are associated with increased expression and/or activity of SK channels in subepicardial myocytes. The possible role of these channels in the structural and functional remodeling of the myocardium of the left ventricle of the heart after ischemia-reperfusion is discussed.



Concentration and composition of circulating vesicles of adipocytic origin in patients with colon polyps and colorectal cancer
Abstract
Extracellular vesicles (EVs) are a heterogeneous population of membrane particles less than 1 μm in size, secreted by various cell types. Most EVs circulating in human blood are particles of platelet, leukocyte, erythrocyte and endothelial origin. The composition of circulating adipocyte EVs in various pathological conditions has been virtually unknown. Small EVs from the blood plasma of patients with colorectal cancer (CRC) and colon polyps with obesity or metabolic syndrome were isolated by ultrafiltration with double ultracentrifugation. To study the composition of adipocyte EVs, immunoprecipitation in combination with Western blotting and flow cytometry were used. Vesicle fractions (FABP4- and CD11b-immunoprecipitated EVs, as well as EVs contained in the supernatant after removal of CD11b-positive EVs) contained a complex of adipocyte markers (FABP4, PPAR-γ and perilipin 1). EVs of monocyte-macrophage origin precipitated on CD11b-coated particles in CRC patients without obesity were characterized by combined overexpression of FABP4 and perilipin 1, while such overexpression was not typical for CRC patients with metabolic syndrome or obesity. The fraction of truly adipocyte vesicles (supernatant after removal of CD11b-positive EVs) was characterized by the presence in all patients of a complex of adipocyte markers with predominant expression of FABP4 in both patients with metabolic syndrome/metabolically healthy obesity and patients without metabolic disorders. To correctly characterize circulating EVs of patients without obesity, it is first necessary to remove the fraction of CD11b-positive monocyte-macrophage EVs from EV preparations by immunoprecipitation or similar methods, and in the supernatant after removal/sorption of precipitated EVs, the composition of adipocyte vesicles can be studied using a set of markers (FABP4, PPAR-γ, perilipin 1, etc.). Moreover, in patients with metabolic disorders, taking into account the insignificant expression of FABP4 in CD11b-immunoprecipitated EVs, preliminary depletion of vesicle preparations is apparently not so necessary.



Immunization of male BALB/c and C57BL/6 mice similar modulates chemical signals detected in both chromatographic and behavioral tests
Abstract
The odor plays a key role in communication between animals and the choice of a mate. The odor of urine of males becomes less attractive to mature females after infection or activation of the immune system. The development of the immune response in the early stages is related with the production of both pro-inflammatory and anti-inflammatory cytokines. To investigate the chemical basis of the observed differences and examine the influence of female interactions with the odor of antigen-treated males, we immunized males of inbred BALB/c (Th1) and C57BL/6 (Th2) mice with hemocyanin (KLH). For females of both tested strains, the attraction of the odor of male urine collected 3 days after immunization was lower compared with the odor of control males. Herewith, BALB/c females sniffed the urine of immunized males less frequently, and C57BL/6 females demonstrated a shorter duration of grooming in olfactory tests with urine of immunized males. The altered response of females to the odor of male urine collected on day 3 after KLH injection matched with antigen-induced modulation of relative levels of volatile organic compounds (VOCs) detected in urine samples by gas chromatography and mass spectroscopy (GC-MS). In males of both strains, after KLH injection, an increase in the content of nonanal, benzothiazole, as well as 2-sec-butyl-4,5-dihydrothiazole, and [1,4,5]-oxadithiepane was shown. At the same time, no compounds were found, the content of which changes in different directions in the urine of males after immunization, depending on the strain of the animal.



Development of Acomys cahirinus in the laboratory conditions
Abstract
The Cairo spiny mouse (Acomys cahirinus) is a unique animal model for studying ontogenesis and regeneration. At the same time, the features of its biology, in particular, the small number of pups in the litter, significantly complicate research work. The aim of the article was to study the behavior and reproduction of the Cairo spiny mice and to create the reproductive nucleus of the colony in our laboratory. This article describes the husbandry of Cairo spiny mice, and techniques of working with them, such as optimizing the diet and housing conditions, handling and marking for individual identification, and also some reproductive parameters of the colony. We have optimized the animal diet by adding dry arthropods, an important component of the spiny mice natural diet, as well as enriched the environment by placing to each cage the running wheels, tunnels and houses. As a result, an increase in the number of animals was obtained by more than 50% over 9 months; the overall survival rate of the offspring was 98%.


