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卷 109, 编号 4 (2023)

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ОБЗОРНЫЕ И ПРОБЛЕМНЫЕ СТАТЬИ

GABAergic Mechanisms of the Brain Tolerance to Hypoxia in Lower Vertebrates

Kolesnikova E.

摘要

Hypoxic/ischemic brain injuries a major medical challenge. One of the approaches to the development of therapeutic interventions is to establish the pathways of survival for neurons in tolerant to O2 deficiency vertebrates, which could suggest the ways to mitigate hypoxic catastrophe for separate cells under oxygen starvation. Metabolic depression is considered to be a universal strategy for the survival of hypoxia tolerant animals; however, the details of the mechanism of brain metabolism limitation with a decrease in PO2 have not hitherto been established. Under oxygen starvation, an increase in the extracellular concentration of inhibitory neurotransmitters can be one of the significant links in the apparatus for suppression of electrical activity, which makes it possible to reduce energy demand. GABA (γ-aminobutyric acid) serves as a universal inhibitory neurotransmitter in the CNS of higher and lower vertebrates, the functioning of which is associated with the metabolism suppression and leveling the consequences of an energy failure. GABA is found in various taxonomic groups of vertebrates. This review considers strategies for GABA involvement in the mechanisms of ensuring a brain tolerance to oxygen starvation in representatives of various taxonomic groups of lower vertebrates (cyclostomes, cartilaginous and bony fish, amphibians, reptiles), which are distinguished by a most pronounced ability to survive under acute and chronic hypoxia/anoxia.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):399-423
pages 399-423 views

ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ

Electrical Stimulation of the Spinal Cord as a Method of Regulation Walking Kinematics in Post-Stroke Patients

Bogacheva I., Shcherbakova N., Moshonkina T., Grishin A., Skvortsov D., Kaurkin S., Gerasimenko Y.

摘要

Multisegmental transcutaneous electrical stimulation of the spinal cord (sсTS), affecting spinal neural networks and motor pools of leg muscles, was used to correct treadmill walking in stroke patients. The study involved 15 patients in the recovery period after acute cerebrovascular accidents. A noninvasive spinal neuroprosthesis with a multichannel stimulator and a system for detecting phases of the walking cycle (“Cosima”, Russia) was used to activate motor pools of leg flexor muscles in the transfer phase, activation of motor pools of extensor muscles in the stance phase in combination with continuous activation of spinal locomotor networks. Using of sсTS during walking on a treadmill increased the amplitude of movements in the ankle joint and the length of the step cycle on the paresis side, as well as decreased the asymmetry of both legs in the phases of the step. The height of the paretic leg lift increased in 80% of patients. With a combination of continuous and phase-dependent stimulation, the increase in the range of motion in the joints was maximal compared to phase-dependent or only constant stimulation. The obtained data demonstrate that the proposed algorithm of the sсTS modulates the parameters of walking movements in patients with the consequences of cerebral circulation accidents and can be considered as a promising method of motor rehabilitation.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):424-437
pages 424-437 views

Exploring the Molecular and Genetic Mechanisms of Action of the α2-Adrenergic Agonist Mafedine in Experimental Traumatic Brain Injury in Rats

Sysoev Y., Shustov M., Prikhodko V., Shitc D., Puchik M., Okovityi S.

摘要

Neurological impairments due to traumatic, vascular, or neurodegenerative brain diseases have a high prevalence worldwide. Among them are motor, cognitive, and mental disorders, which have a serious negative impact on the working and social activities of the patients. This calls for the search and development of novel effective neuroprotective agents. Previous studies have shown the pyrimidine-derived α2-adrenergic agonist mafedine to be highly effective for the amelioration of neurological deficits in experimental traumatic brain injury (TBI) in rats. Despite the results of the previous works favouring the major role of the α2 adrenergic receptor activation in the mechanism of action of mafedine, the search for additional molecular targets is an important part of the development of any drug to be used in clinical practice. In this work, we evaluated the effects of 7 day-long course administration of mafedine (2.5 mg/kg b.w.) on the expression of brain-derived neurotrophic factor (BDNF), the proinflammatory cytokines interleukin (IL)-1β, -6, tumour necrosis factor (TNF)-α, and the α2A, α2B, and α2C α2-adrenergic receptor subtypes in the brain cortex of rats subjected to TBI, using the reverse-transcription real-time polymerase chain reaction method. TBI was modelled by the controlled cortical impact technique in an open area of sensorimotor cortex of the left brain hemisphere. Behavioural alterations in the injured animals were assessed in the Open field test, and the fore- and hindlimb motor function, in the Limb placing, Cylinder, and Beam walking tests. Our experiments show that TBI causes severe motor impairments as well as decreases exploration in rats. Besides, at post-TBI day 7, a reduction in the expression of all analyzed genes is seen, which is the most pronounced in the contralateral (uninjured) hemisphere. Course administration of mafedine (2.5 mg/kg b.w.) resulted in moderate stimulation of the injured rats’ behaviour, increased exploratory activity compared to controls, and improved sensorimotor deficit as assessed by the Beam walking test. Gene expression analysis results indicated that mafedine decreased α2B-adrenergic receptor, TNF-α, and IL-6 expression in the injured hemisphere. At the same time, compared to rats with TBI having received no treatment, mafedine-treated animals exhibited higher α2B-adrenergic receptor and IL-1β expression in the injured rather than the intact hemisphere. These results confirm the previously observed neuroprotective activity of mafedine and imply that it may exert its effects via suppression of α2B-adrenergic receptor and proinflammatory cytokine expression in the injured brain hemisphere, at the same time increasing their expression in the intact one.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):438-456
pages 438-456 views

Features of Changes in the Velocity Indicators of Cerebral Blood Flow in Rats at Different Stages of Aging

Gorshkova O.

摘要

Changes in the velocity of cerebral blood flow can make a significant contribution to the formation of age-related cerebrovascular diseases. The age-related changes in the velocity indicators of cerebral blood flow in rats at different stages of aging were studied. Using Doppler ultrasound the state of blood flow in the cortex and subcortical structures of the cerebral hemispheres was analyzed by the value of linear velocities and blood flow indexes in young Sprague-Dawley 4-month-old and aging 18 and 23-month-old rats. It has been established that aging is accompanied by changes in the parameters of cerebral blood flow in the cortex and subcortical structures of the rat brain. Changes develop gradually and differ at different stages of aging. By 18 months, perfusion in the frontal and parietal regions hemispheres of the brain increases due to an increase in peak and mean velocity per cardiac cycle and a decrease in the level of resistance of cerebral vessels. These processes precede the development of subsequent hypoperfusion disorders of blood flow observed at later stages of aging. Hypoperfusion changes in 23-month-old rats are most pronounced in the frontal region of the cerebral hemispheres and are characterized by a decrease in peak velocities and an increase in blood flow indexes.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):457-465
pages 457-465 views

Immunohistochemical Study of Macrophages of Sciatic Rat Nerve after Damage and Subperineural Injection of Mesenchymal Stem Cells

Petrova E., Kolos E.

摘要

The dynamics of the processes of Wallerian degeneration in the Wistar-Kyoto rat sciatic nerve after injury (ligation, 40 s) was studied.The density of Iba-1+ macrophages and the state of myelin fibers stained with Luxol strong blue in the distal segment of the nerve at different times after injury were studied. Parts of rats were subperineurally transplanted with MSCs from the bone marrow of Wistar-Kyoto rats. It was shown that the highest distribution density of macrophages in the distal segment of the nerve was observed 7 days after surgery. The use of cell therapy leads to a decrease in the number of macrophages during this period and to a delay in the demyelination of damaged nerve fibers. Sixty days after the operation, the macrophage population density and the number of remyelinated regenerating nerve fibers of the distal nerve segment did not differ in control (ligature) and experimental (ligature and MSC injection) animals. The molecular mechanisms of the noted changes in the early stages after injury require further research.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):466-476
pages 466-476 views

Changes in Behavioral Characteristics and Tyrosine Hydroxylase Levels in the Nucleus Accumbens of the Brain of DAT-HET Rats during Free Alcoholization

Antonova I., Kucher E., Filatova E., Veraksa A., Morina I., Zavyalov V., Egorov A.

摘要

DAT-HET rats with their underlying hyperdopaminergia are a promising model for the investigation of neuropsychiatric diseases, which are based on impaired dopamine neurotransmission, including alcoholism. The aim of the work was to evaluate the effect of free alcoholization on drinking, locomotor, exploratory behavior, anxiety, and Tyrosine hydroxylase (TH) levels in rats with impaired functioning of the DA system (DAT-HET). The study was carried out on adult male rats of the DAT-HET (n = 15) and Wistar (n = 13), which were divided into 4 groups: “DAT-HET ethanol” (n = 10) and “Wistar ethanol” (n = 9), who were in the mode of free alcoholization for 112 days of the experiment. The DAT-HET water (n = 5) and Wistar water (n = 4) groups did not have access to an ethanol solution and did not participate in behavioral tests. Ethanol preference and consumption was assessed in the “Two-bottle test”. The amount of ethanol consumed in the cells was recorded weekly. Behavior was assessed using the Open Field and Elevated Plus Maze tests. After alcoholization, to assess the level of TH, an immunohistochemical (IHC). It was found that during free alcoholization, DAT-HET rats do not form preferences for ethanol. Under the low ethanol consumption, the initial hyperactivity in DAT-HET rats is leveled. The DAT-HET model leads to an increase in TH levels in NAcc. In addition, the free alcoholization reduces the level of TG in NAcc with the development of a pathological increase in TH, observed in the DAT-HET model, but has no effect on healthy animals.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):477-488
pages 477-488 views

Spectral Characteristics of Cardinal Vowels as Indicators of the Auditory Speech Feedback Control in Patients with Moderate and Moderately Severe Chronic Postlingual Sensorineural Hearing Loss

Shtin K., Lunichkin A., Gvozdeva A., Golovanova L., Andreeva I.

摘要

Chronic sensorineural hearing loss (SNHL) is characterized by an increase in hearing thresholds at basic speech frequencies, which implies the auditory speech feedback control worsening and, as a result, changes of speech characteristics. A hypothesis was tested that such worsening can manifest itself in an increase of F0, F1, F2 formants of speech vowel sounds in patients with moderate and moderately severe postlingual SNHL. Recordings of elicited speech were performed for young and middle age women (36–59 years): 7 women speakers with moderate SNHL who did not use hearing aids; 5 women speakers with moderately severe SNHL who were hearing aid users but were not using them during the recordings; a control group of 12 normally hearing women speakers. An assessment of F0, F1 and F2 of stressed vowels [a], [i], [u] and calculations of vowels’ centralization indices – vowel space area, vowel formant centralization ratio and the second formant ratio (F2i/F2u), were performed. All the studied spectral indices in groups of patients with postlingual SNHL were similar to those in the control group, no statistically reliable differences were revealed.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):489-501
pages 489-501 views

The Maintenance of AMPK Activity Eliminates Abnormally Accelerated Differentiation of Primary Myoblasts Isolated from Atrophied Rat Soleus Muscle

Vilchinskaya N., Mirzoev T., Shenkman B.

摘要

Mechanical unloading of skeletal muscles leads to the development of atrophic processes and a decrease in the total number of satellite cells (SCs) that are involved in muscle regeneration. In vitro studies revealed an increased differentiation of myoblasts derived from rat soleus muscle after an unloading-induced decrease in AMP-activated protein kinase (AMPK). AMPK is necessary for the activation of SCs and also participates in the regulation of myoblast proliferation and differentiation. It can be assumed that a decrease in the activity of AMPK after mechanical unloading can contribute to the acceleration of myoblast differentiation. The main purpose of this study was to elucidate a possible role of AMPK in the regulation of differentiation of myoblasts isolated from rat soleus muscle after mechanical unloading. To test this hypothesis, a specific AMPK activator, AICAR, was used to prevent a decrease in AMPK activity during differentiation of myoblasts isolated from rat soleus muscle after 7-day unloading. Immunocytochemistry, PCR-RT and Western blotting were used to assess changes during myoblast differentiation. In differentiating myoblasts derived from the unloaded soleus muscle there was a significant decrease in AMPK (Thr172) and ACC (Ser 79) phosphorylation levels, an increase in myotube differentiation index, myoblast fusion factors and the expression of myogenic regulatory factors (MRF). Furthermore, there was a decrease in the expression of slow myosin heavy chains (MyHC) and an increase in the expression of fast MyHC isoforms. AICAR treatment of differentiating myoblasts obtained from the unloaded soleus muscle prevented a decrease in AMPK and ACC phosphorylation, returned the expression levels of MRF and fast isoforms of MyHC to the control levels as well as maintained the expression of slow MyHC. Thus, abnormally accelerated differentiation of myoblasts isolated from atrophied rat soleus muscle can be compensated by maintaining the control levels of AMPK activity using AICAR.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):502-516
pages 502-516 views

Role of L-Type Calcium Channels in the Increased Fatigue of Rat Soleus Muscle under Functional Unloading

Sharlo K., Lvova I., Tyganov S., Sidorenko D., Shenkman B.

摘要

Excessive long-term accumulation of calcium ions in the myoplasm of skeletal muscles can negatively affect mitochondria and lead to muscle dysfunction. The aim of our study was to identify the role of L-type calcium channels in the development of increased fatigue rat soleus muscle under functional unloading. Young male Wistar rats were divided into three groups of 8 animals each: the vivarium control group (C), the group subjected to hind limb unloading for 7 days (7HS) and the group with 7 days of hindlimb unloading with daily intraperitoneal injections of nifedipine (7 mg/kg body weight). The administration of nifidipine during hindlimb unloading prevented the upregulation of calcium-dependent phosphorylation of calcium-calmodulin kinase II (CaMK II), prevented the increase in fatigue and contributed to the preservation of mitochondrial proteins, DNA and mRNA expression of a number of genes that regulate mitochondrial biogenesis.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):517-529
pages 517-529 views

Research of the Expression of IL-13 Receptors and IL-13R Genes in the Bronch of Rats with Ovalbumin-Induced Bronchial Asthma

Blazhevich L., Smirnova O., Kirilina V., Maslyukov P.

摘要

This article presents the results of studies of the levels of expression of the IL13R gene and the levels of expression of the molecular IL13R in the bronchi of control rats and rats with ovalbumin-induced asthma. The choice of these receptors is due to the great importance of these structures in the pathogenesis of allergic bronchial asthma. Biological materials of 64 Wistar rats were studied using real-time PCR and immunohistochemical methods. As a result of the studies, it was found that under conditions of asthma development in the tissues of the bronchi of rats, a pronounced expression of the IL13R genes, a significant expression of the molecular receptor for interleukin-13, occurs. In bronchi with an intramural ganglion (bifurcation zone), the level of IL13R gene expression and the level of expression of the IL13R molecular receptor were significantly higher than in tracheal samples without ganglia. Sodium cromoglycate, administered to rats 5 hours after the last inhalation of ovalbumin, led to a decrease in the mRNA content in the bronchi of animals compared to animals that did not receive mast cell stabilizer treatment.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):530-544
pages 530-544 views

The Effect of Prolonged Emotional and Painful Stress on the Expression of Proinflammatory Cytokine Genes in Rats with High and Low Excitability of the Nervous System

Shalaginova I., Tuchina O., Turkin A., Vylegzhanina A., Nagumanova A., Zachepilo T., Pavlova M., Dyuzhikova N.

摘要

Stress plays an important role in the pathogenesis of anxiety and depressive disorders. Neuroinflammation is considered as one of the mechanisms by which stress alters the molecular and cellular plasticity in the nervous tissue, which leads to a violation of the functions of the central nervous system. The contribution of genetically determined features of the nervous system to the development of post-stress neuroinflammation has not been sufficiently studied. In this study, the dynamics of poststress changes in the mRNA levels of the il1ß and tnf genes of proinflammatory cytokines interleukin-1-beta (IL-1ß) and tumor necrosis factor (TNF) in the blood and in the brain in two rat strains with high and low excitability thresholds of the nervous system (HT and LT) was evaluated. Changes in IL-1ß and TNF mRNA levels were assessed by real-time PCR 24 h, 7, 24 and 60 days after prolonged emotional and painful stress in the blood and three brain structures involved in the development of post-stress pathology (prefrontal cortex, hippocampus, amygdala). In highly excitable rats of the LT strain, the level of IL-1ß mRNA in the hippocampus and amygdala increased compared to the control 24 days after the end of stress, in low-excitable animals of the HT strain, an increase in the level of IL-1ß mRNA was detected only in the hippocampus at the same time. The TNF mRNA level did not change in any of the strains at any of the time points after stress. Genetically determined excitability of the nervous system is a promising marker of individual vulnerability to stress, manifested in post-stress disorders associated with the characteristics of the formation and dynamics of neuroinflammation.

Rossijskij fiziologičeskij žurnal im. I.M. Sečenova. 2023;109(4):545-558
pages 545-558 views
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