Ашық рұқсат
Рұқсат берілді
Тек жазылушылар үшін
Том 110, № 2 (2024)
EXPERIMENTAL ARTICLES
Time scale of adaptation at the tonal sequence processing in the awake mice auditory cortex neurons
Аннотация
The study was firstly carried out on stimulus-specific adaptation of neurons in the primary and anterior fields of the awake house mice auditory cortex to sound sequences of four 100-ms tonal signals, with frequency of tones corresponding to the neuronal characteristic frequency, and also with the inter-tone interval constant for one sequence and varying from 0 to 2000 ms in different sequences. The analysis of the data obtained showed the adaptation effect in the responses of all studied primary auditory cortex neurons, which was observed as the absence or significant decrease in activity evoked by the components of a series of tones following the 1st, at inter-stimulus intervals of 0–500 ms. A quantitative assessment of the adaptation effects as a function of inter-stimulus intervals within the tonal sequence, performed over whole population of studied neurons, showed that the individual time scales of adaptation of neurons varied significantly, which may be crucial for the formation of optimal time windows for the processing of grouping and separation of sound events, which are important both for perception of animal vocalizations and human speech.
157-168
Effect of genetically engineered drugs in aseptic necrosis of the femoral head in rats
Аннотация
Bone tissue is a dynamic structure with a metabolic function. The maintenance of bone homeostasis is carried out due to the continuous process of its renewal, remodeling. At the same time, a number of pathological processes, such as ischemic catastrophe, can lead to a violation of the balance of maintaining the constancy of the bone structure. One of these diseases is aseptic necrosis of the femoral head. The presented study analyzes the dynamics of expression of genes involved in maintaining bone tissue homeostasis, changes in the histological picture during the development of aseptic necrosis of the femoral head in laboratory rats that did not receive genetically engineered drugs and against the background of the use of inhibitors of biological action IL-6, TNF-α. After induction of aseptic necrosis in the proximal epiphysis of the femur, the histological picture in animals of different groups was not the same. More preserved bone architectonics and a larger volume of bone plates were recorded in rats receiving genetically engineered drugs compared to animals without the introduction of biological agents. The latter also had the most vivid picture of osteodestruction with increased expression of proinflammatory cytokine genes. In animals, against the background of the use of drugs of inhibitors of the biological action of IL-6, TNF-α, from the second week after induction of aseptic necrosis of the mRNA, the profile of the spongiose bone of the proximal epiphysis of the femur tended to increase the expression of osteoreparation genes. At the same time, the greatest inhibition of osteoclastogenesis gene expression was obtained in rats after injection of a monoclonal antibody to the IL-6 receptor.
169-184
Lombard speech detection in case of spatial separation between noise source and talkers of different genders
Аннотация
The spatial selectivity of hearing to speech signals was studied when the target signal and interference were separated by distance between their sources and the listener. In the work, the hypothesis about the improvement of hearing selectivity due to more intensive activation of the high-frequency binaural mechanism due to the shift of the speaker’s voice spectrum occurs in noisy environment towards high frequencies, was tested. The thresholds for detecting the target signal – a two-syllable word uttered by male or female, were evaluated in the two-alternative two-interval forced choice paradigm in 4 series. Series differed by the type of target signal (ordinary or Lombard speech) and the location of target source and noise (multi-talker noise) one. The both sources were located at a distance of 1 and 4 m opposite the subject at the level of his head. The detection threshold was defined as the ratio of signal and noise levels at the listener’s place (S/N). The threshold for detecting the target signal (male and female speaker voices together) was -11 dB S/N for ordinary as well as Lombard speech. It did not depend on which of the sources - the target signal or noise, was closer to the listener. In normal speech, the detection thresholds on average differed for male and female voices, but the difference was not significant. In Lombard speech, these thresholds were significantly different: for a male voice, the threshold at a detection level of 0.67 was -10 dB S/N, and for a female voice – -12.5 dB S/N.
185-195
BDNF prodomain inhibits neurotransmitter quantal release in mouse motor synapses with the necessary participation of sortilin and adenosine A1-receptors
Аннотация
Brain neurotrophin (BDNF) is synthesized by proteolysis of proneurotrophin to form mature BDNF and the prodomain, whose regulatory activity on neuromuscular transmission is just beginning to be studied. At motor synapses, the BDNF prodomain has an inhibitory effect, stimulating GIRK potassium channels via activation of p75 receptors. The aim of this work was to study was to study the initiation and implementation of the mechanism of inhibitory action of the BDNF prodomain in mature motor synapses of the mouse diaphragm. Microelectrodes were used to record spontaneous (miniature) and multiquantal endplate potentials evoked by stimulation of motor axons (MEPP and EPP, respectively). Using selective antagonists, it was revealed that the inhibitory effect of the prodomain on synaptic transmission requires the participation of sortilin, but not TrkB receptors. Stimulation of GIRK induced by the prodomain requires the participation of synaptic metabotropic receptors, which ensure the action of βγ-subunits of Gi proteins on GIRK. Using selective inhibitors, it was found that M2 cholinergic receptors and P2Y13 purinoceptors negatively regulate presynaptic L-type calcium channels, but these metabotropic receptors are not functionally related to the action of the BDNF prodomain. It turned out that the inhibition of quantal release of acetylcholine in motor synapses caused by BDNF prodomain requires the activity of the adenosine A1-receptors only. In addition, when pannexin 1 was pharmacologically blocked by probenecid, the BDNF prodomain lost its inhibitory effect on neuromuscular transmission. Thus, BDNF prodomain-induced inhibition of quantal neurotransmitter release in mouse motor synapses requires the participation of sortilin and endogenous activation of adenosine A1-receptors, which requires the functioning of pannexins 1, which most likely provide an additional source of synaptic ATP to the vesicular one.
196-215
Cobalt microinjections into the infralimbic cortex of the anesthetized rat suppresses circulatory and respiratory reactions to the microelectrostimulation of the lateral orbital cortex
Аннотация
The central autonomous network that controls visceral systems, including circulatory and respiratory systems, includes the visceromotor infralimbic cortex (IL), which is one of the areas of the prefrontal cortex and is located on the medial surface of the large hemispheres. At the same time, there is evidence that areas of the prefrontal cortex located on the orbitofrontal surface, including the lateral orbital cortex (LO), can participate in the control of autonomous functions. The purpose of this work was to experimentally test the hypothesis according to which the participation of LO in the control of respiratory and circulatory functions is realized through IL. To this end, in acute experiments on laboratory rats anesthetized with urethane, the effect of microinjections of cobalt chloride solution (CoCl2) in IL on the reactions of circulatory and respiratory systems caused by microelectrostimulation of LO was investigated. It is known that Co2+ ions are non-specific blockers of synaptic transmission, therefore microinjections of CoCl2 solutions lead to disruption of conduction in the structures of the central nervous system. In the first, control series of experiments, micro-electrical stimulation of LO caused specific responses of the circulatory and respiratory systems, which were consistently reproduced throughout the experiment. In the second, experimental series, the introduction of CoCl2 solution into IL suppressed responses to micro-electrical stimulation of LO, and this effect turned out to be reversible. The obtained results confirmed the hypothesis put forward about the possible participation of IL in the implementation of autonomous LO functions. The elucidation of the mechanisms that ensure the interaction of LO and IL in the context of autonomous control should be the subject of further experimental research.
216-229
Methods for assessing the diastolic distensibility of the left ventricle
Аннотация
The most important property of the myocardium that determines the filling of the left ventricle (LV) of the heart is its distensibility. The simplest method of its assessment is the ratio of pressure and LV volume at the end of the diastole. Active relaxation of the myocardium is determined by the work of calcium pumps, and passive relaxation is determined by sarcomere proteins and, first of all, by connectin – titin. The paper compares 6 calculated indices of LV diastolic stiffness of the heart, compares their stability, variations and correlation coefficients from various parameters of hemodynamics. It is shown that only the diastolic stiffness index No. 4, which takes into account LV stiffness at the beginning and end of diastole, showed a weak dependence on LV, heart rate and other parameters of LV hemodynamics of the heart. Therefore, this index can be used in the future to assess the distensibility of the heart in various pathologies.
230-237
Influence of long-term social isolation on the behavior and dopamine system of the brain in mice
Аннотация
The dopamine brain system is involved in the regulation of various physiological processes and behavioral responses, including social behavior. It was shown in rodents that prolonged social isolation can lead to changes in behavioral parameters and neurochemical parameters, but these data remain unclear. In this work, we studied the effects of prolonged social isolation on the behavior and state of the brain dopamine system in male C57Bl/6 mice. Animals of the experimental group from the age of 40 - 42 days were kept individually in separate cages for six weeks, while the mice of the control group were kept in-group conditions. Isolation did not affect locomotor and exploratory activity in the “open field” test compared to the content in the group. At the same time, animals subjected to prolonged isolation demonstrated a longer duration of social contacts in the “resident-intruder” model and a weakening of stereotypical behavior in the “marbles burying” test compared to the control group. These behavioral changes were accompanied by an increase in mRNA levels of the genes encoding dopamine D1 and D2 receptors in the striatum of mice. In addition, the level of the dopamine metabolite DOPAC decreased in the hypothalamus and increased in the frontal cortex of mice due to the effect of social isolation compared with the control group. The results contribute to the understanding of the effects of prolonged social isolation on the behavior and dopamine brain system in mice.
238-253
Effect of dietary phospholipid on the behavior in C57BL/6J mice
Аннотация
Nowadays phospholipids are widely used as hepatoprotective, neuroprotective and anti-stress drugs, as well as the dietary supplements. Besides, lecithin consisting up to 70% of the phospholipids mixture: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidic acid, is the often component of food production as an emulsifier. Dose of these biologically active substances in the modern human diet could be quite high. Previously we have shown that chronic intestinal inflammation in Muc2-knockout mice induces behavioral changes along with the significant increase in the content of phospholipids in intestinal epithelial cells, particularly, phosphatidylcholine, phosphatidylserine and phosphatidic acid. Here we investigate the effects of long-term administration of a mixture of these phospholipids, as well as the effects of long-term administration of soy lecithin on the behavioral patterns in laboratory mice. Animals long-term taken a phospholipid mixture shows no normally observed preference towards females in the two intruders test (with female and male). In the social odor preference test, they also did not distinguish female and male odors, while non-social odors discrimination preserved. In addition, we identified a decrease in anxiety, obsessive traits, and schizophrenia-like behavior traits in these animals. Soy lecithin supplementation had similar effects on social behavior and compulsive traits, and increased aggression in males. Thus, long-term perinatal administration of either mixture of phospholipids (phosphatidylcholine, phosphatidylserine and phosphatidic acid) or soy lecithin can influence various aspects of behavior in mice.
254-267
Features of reactions to stress in rats with passive-defense behavior after light desynchronosis and physical activity
Аннотация
An assessment was made of hematological parameters of peripheral blood and structural and functional changes in the adrenal glands in stress-unresistant rats (passive-defensive type of behavior in the open field test) after exposure to light deprivation and physical activity during the spring equinox. The experiment showed that light deprivation for 10 days reduces the total number of leukocytes, the absolute content of monocytes, granulocytes, lymphocytes and the level of corticosterone in the peripheral blood compared to the intact group, that was on a natural lighting regime. Histological analysis of the adrenal glands of this group showed, that in the zona fasciculata under such conditions there was nuclear hypertrophy, an increase in the nuclear-cytoplasmic ratio of adrenocorticocytes and a decrease in the size of the zona glomerulosa of the adrenal cortex of rats in relation to the intact group. Physical activity in the form of forced swimming until complete fatigue for 5 days in a row in natural light in stress-unresistant rats did not change the parameters of the peripheral blood of animals, however it led to an increase in the area of the cytoplasm, the nuclear-cytoplasmic ratio, as well as the formation of hypertrophy of the nuclei of adrenocorticocytes in the fascicle adrenal zones, which indicated the preparation of cells for increased synthetic activity. Keeping rats for 10 days in complete darkness before forced swimming every day for 5 days, on the one hand, formed a hypoxic state and exhaustion of the adrenal glands, on the other hand, stabilized the leukocyte pool of peripheral blood compared to similar indicators in intact rats.
268-282
Desmin degradation in the skeletal muscle of patients with chronic critical illness
Аннотация
Critical illness myopathy (CIM) is a primary myopathy that develops in critically ill patients. Histologic features of CIM include a general decrease in muscle fiber cross-sectional area and a predominant loss of the motor protein myosin. These features are observed in the absence of inflammatory infiltrates but with detectable cytokine activation. The purpose of this study was to examine the state of the extracellular matrix of the human soleus muscle under conditions of CIM caused by chronic impairment of consciousness. Incisional muscle biopsies were taken from the soleus muscle of 6 patients who were in a chronic critical condition and were treated in the Department of Anesthesiology and Reanimation at the A.L. Polenov Russian Research Institute - branch of the Almazov National Medical Research Center. The study included patients with a chronic impairment of consciousness lasting at least 2 months. Muscle biopsies taken from healthy men were used as controls. The biopsies were obtained using needle biopsy under local anesthesia. Using histological staining of tissue sections, it was determined that patients with CIM exhibited a significant increase in collagen area, surpassing the control value by 82%. An increased mRNA content of collagens I, III, and VIa was also observed, along with an increase in the protein content of collagen I and III. At the same time, we did not observe any changes in the content of fibronectin and extracellular tissue growth factor mRNA. However, we did observe an increase in the mRNA of the integrin A7 subunit. The results obtained indicate significant skeletal muscle fibrosis under CIM conditions. Further studies on the signaling pathways that regulate this process are needed.
283-296