Effect of melanocortin neuropeptides on the level of apoptotic and neurotrophic factors under «social» stress
Background: Currently, scientific papers reflecting the results of studying the pathological influence of stress factors, including "social" stress, on various body systems are of particular interest. It has been proven that prolonged exposure to stress contributes to the formation of various types of disorders, which ultimately leads to the development of violations of the molecular and cellular mechanisms of programmed cell death. In this connection, close attention is currently being paid to assessing the role of apoptotic and neurotrophic factors in the implementation of a stress reaction. The aim of the study: To study the effect of melanocortin neuropeptide compounds on the level of apoptotic (caspase-3, caspase-8, TNF-α) and neurotrophic (BDNF, NGF) factors in the blood serum of white rats under conditions of "social" stress. Materials and methods: Experimental studies were carried out on 70 nonlinear white male rats 6 months of age. In the process of modeling "social" stress, all rats were divided by type of behavior into "aggressors" and "victims". Experimental groups (n = 10) were formed in the study: control animals; animals exposed to stress for 20 days; groups of rats treated intraperitoneally at a dose of 100 mcg/kg/day, starting from the 1st day of exposure to the stress factor, with a course of 20 days, glyproline compounds ACTH(4-7)-Pro-Gly-Pro (Semax) and ACTH(6-9)-Pro-GLY-Pro. The effect of the compounds on the level of apoptotic and neurotrophic factors was assessed by determining the level of caspase-3, caspase-8, tumor necrosis factor, nerve growth factor and brain neurotrophic factor of white rat blood serum by enzyme immunoassay. Results: The study revealed that under conditions of "social" stress, an increase in apoptotic processes was observed, accompanied by an increase in the level of caspase-3, caspase-8, TNF-α in the blood serum of white rats and a decrease in the concentration of BDNF and NGF. The introduction of melanocortin neuropeptides against the background of stress contributed to the restoration of the level of the studied indicators, which is most likely due to the presence of antiapoptotic and neuroprotective effects in melanocortins due to inhibition of the caspase-dependent cascade of apoptosis reactions, as well as induction of the synthesis of neurotrophic factors with antiapoptotic activity. Conclusion: Thus, the introduction of melanocortin neuropeptide compounds ACTH(4-7)-Pro-GLY-Pro (SEMAX) and ACTH(6-9)-Pro-GLY-Pro under stress conditions contributes to the restoration of the level of caspases and tumor necrosis factor, as well as neurotrophic factors, resulting in an anti-apoptotic effect due to inhibition of the caspase-dependent cascade of reactions.
Yasenyavskaya AL, Tsybizova AA, Andreeva LA, et al. Effect of melanocortin neuropeptides on the level of apoptotic and neurotrophic factors under «social» stress. Research Results in Biomedicine. 2022;8(3):398-411. Russian. DOI: 10.18413/2658-6533-2022-8-3-0-10
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