卷 52, 编号 3 (2016)

The brain leptin signaling system plays a key role in the regulation of feeding behavior, peripheral metabolism, functions of the nervous and endocrine systems; its abnormalities lead to metabolic disorders, including metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). This system is activated by leptin, which is produced by adipocytes and then penetrates into the brain through the blood–brain barrier, where leptin binds to leptin receptors OBRb. This leads to an activation of tyrosine kinase JAK2, which phosphorylates tyrosine-containing sites located in the cytoplasmic domain of the receptor, resulting in stimulation of phosphatidylinositol-3-kinase, transcription factors STAT3 and STAT5, phosphatase SHP2 and mitogen-activated protein kinases. Reduction in the number of functionally active leptin receptors and abnormalities in the downstream components of leptin cascades in nerve cells lead to leptin resistance. Since the leptin system in hypothalamic neurons is closely interrelated with the insulin, melanocortin, dopaminergic and other signaling systems, leptin resistance induces multiple functional disorders in the CNS and at the periphery. Restoring the brain leptin system functions is one of the promising approaches to treat and prevent metabolic disorders, including MS and DM2. This review addresses the structural-functional organization of the leptin signaling system, its functional interaction with other brain signaling systems, causes and consequences of central leptin resistance as well as approaches aimed at restoring leptin functions in hypothalamic neurons under MS and DM2.

Inotropic effects of yttrium acetate (Y³⁺) on contractions of myocardium preparations of the frog Rana ridibunda, as well as on respiration and the inner membrane potential (ΔΨ_mito) of isolated rat heart mitochondria were studied. 2 mM yttrium in Ringer solution was found to significantly reduce the amplitude of myocardium contractions, evoked by electric stimulation, and increase the half-relaxation time (n = 5). In experiments with Ca²⁺, Y³⁺ decreased the Ca²⁺-dependent basal respiration rate in rat heart mitochondria, energized by glutamate and malate, impeded the reduction in respiration of these mitochondria operating in state 3 after Chance or uncoupled by 2,4-dinitrophenol, and inhibited a Ca²⁺-induced reduction in their inner membrane potential. The data obtained are important for better understanding the mechanism underlying Y³⁺ effects on the myocardial Ca²⁺-dependent processes. Possible mechanisms of the negative inotropic effect of Y³⁺ on myocardium and its influence on the Ca²⁺-dependent processes in rat mitochondria are discussed.

To verify if the peptide preparation Cortexin can be used to correct pathological processes in the CNS during perinatal ontogenesis, a set of physiological parameters (EMG, ECG, respiration, vagosympathetic balance) were recorded and analyzed in a rat perinatal hypoxic-ischemic brain damage (PHIBD) model and control infant rats. In experimental 7-day-old animals, PHIBD was modeled under inhalation ether anesthesia by ligation of the left common carotid artery and subsequent exposure to a gas mixture of 8% oxygen and 92% nitrogen. 1 h after exposure, animals were first injected intraperitoneally with cortexin (1 mg/kg); the preparation was then injected at a daily basis for 10 days. Both control animals and those after surgery but non-treated were injected with physiological solution. After 10 and 30 days after surgery, animals exhibited a delayed body weight gain versus control and significant differences in EMG intensity and spectral structure. Cortexin treatment induced on day 10 a transient improvement in EMG spectral structure but not amplitude; by day 30, the positive effect of cortexin was no longer observed. The respiration rate both in treated and non-treated animals was higher than in control. No significant changes in the heart rate were revealed in animals with PHIBD, but non-treated animals exhibited on day 30 a tendency towards its decrease. The heart rate variability (HRV) analysis showed that 10 days after trauma both non-treated and cortexin-treated animals exhibited a statistically significant shift in the vagosympathetic balance towards a parasympathetic prevalence. On day 30, cortexin treatment yields positive effects, while in non-treated animals the vagosympathetic balance shifts towards a humoral-metabolic and sympathetic prevalence. Cortexin injection to intact rats leads to significant disturbances in the vagosympathetic balance, cardiac and, to a lesser extent, respiratory rhythms, and can cause stable disturbances in activity of the somatic and vegetative nervous systems.

The role of orexin in the organization of the sleep–wake cycle (SWC) is well known. The aim of this study was to examine the timing of the orexinergic system formation in rat postnatal ontogenesis and to assess the role of orexin A in the SWC organization under normal conditions and after prenatal hypoxia undergone on days 14 and 19 of embryogenesis. The SWC was investigated in 30-day-old rats with electrodes implanted into the somatosensory and occipital cortex. Immunoreactivity within the orexigenic structures of the lateral hypothalamus was analyzed. It was shown that in control 14-day-old animals the orexinergic structures were in their formative stage, whereas in 30-day-old rats they were already as formed as in adults. In 14-day-old rats, prenatal hypoxia evoked retarded formation of the orexinergic system. In 30-day-old animals, hypoxia undergone in the prenatal period increased the activity of the orexinergic system, which was higher in animals exposed to hypoxia on day 19 than on day 14 of gestation. In 30-day-old rats, these changes were reflected in the SWC formation in the form of shorter slow-wave sleep, more fitful sleep and increased number of transitions from slow- to fast-wave sleep. The results obtained are discussed in the light of the adaptive-compensatory role of the orexigenic system in postnatal ontogenesis after prenatal damage to the central nervous system.

Development of mycoses and progress of humoral and cellular immune responses were compared in larvae of the Colorado potato beetle Leptinotarsa decemlineata infected with entomopathogenic fungi Metarhizium robertsii, M. brunneum and M. pemphigi. The larvae were found to be highly susceptible to the strains of M. robertsii and M. brunneum but weakly responsive to M. pemphigi. The extent of susceptibility to the pathogens was not related to the stimulating effect of epicuticular extracts on fungal growth. Metarhizium pemphigi, which is non-specific to the Colorado potato beetle, did not cause any significant changes in the immune response and did not colonize the hemocoel. When infected with M. robertsii and M. brunneum, the larvae exhibited an increase in hemocyte count during the early stage of mycosis (day 2) followed by a drastic decrease on day 3. The immunocompetent cells, plasmatocytes and granulocytes, exhibited the greatest decrease. Elevated phenoloxidase activity was recorded in the hemolymph and cuticle on days 2 and 3 post-infection. These changes in the immune responses correlated with strain-specific virulence. Thus, the immune response in Colorado potato beetle larvae is an important factor, which determines differences in the development of mycoses caused by different Metarhizium species.

The morphometric characteristics of the following immature erythroid cells in circulating blood of the round goby (Neogobius melanostomus P.) were studied: late basophilic normoblasts (BN), polychromatic normoblasts (PN): normocytes (mature erythrocytes). The linear dimensions of the blood cells were evaluated on photographs in a computer program ImageJ 1.44p. The longitudinal and transverse axes of the cell and its nucleus were measured. Using appropriate algorithms, the following parameters were calculated: shape index (SI), volume (V_c), area (S_c), thickness (h), and specific surface area (SS_c) of cells and nuclei as well as the nuclear–cytoplasmic ratio (NCR). Major changes were found to occur at the stage of PN → normocytes, being aimed at improving the respiratory characteristics of cells. In addition to accumulating hemoglobin in the cytoplasm and suppressing functional activity of the nucleus, a significant increment in the diffusion surface of erythroid cells was noted. As compared to BNs, S_c and SS_c of normocytes increased by 40 and 17%, respectively, while the cells assumed an ellipsoid shape. The processes underlying the formation of the mature erythrocyte cytoskeleton are discussed.