EFFECT OF GLYPROLINES ON THE LEVEL OF APOPTOTIC AND NEUROTROPHIC FACTORS UNDER CONDITIONS OF “SOCIAL” STRESS

A. Yasenyavskaya, A. Tsibizova, L. Andreeva, N. Myasoedov, O. Bashkina, M. Samotrueva
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Abstract

The aim of the article was to study the effect of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu, on the level of apoptotic factors (caspase-3, caspase-8, the tumor necrosis factor) and neurotrophic factors (the nerve growth factor and the brain neurotrophic factor) in the blood serum of white rats under the experimental modeling of “social” stress.Materials and methods. The experimental studies were carried out on 90 nonlinear white male rats aged 6 months. By the type of behavior, in the process of “social” stress modeling, all the rats were divided into “aggressors” and “victims”. In the study, the following experimental groups (n=10) were formed: control individuals; groups of the rats exposed to stress for 20 days; groups of the animals treated intraperitoneally at the dose of 100 μg/kg/day, starting from the 1st day of the stress factor exposure, with a course of 20 days of glyproline compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu. The effect of the compounds on the level of apoptotic and neurotrophic factors was assessed by determining the level of caspase-3, caspase-8, the tumor necrosis factor, the nerve growth factor and the brain neurotrophic factor of white rat blood serum by enzyme immunoassay.Results. According to the results of the study, it was found out that under the conditions of “social” stress, there was an increase in the apoptotic processes accompanied by an increase in the level of caspase-3, caspase-8, TNF-α in the blood serum of white rats, as well as a decrease in the concentration of neurotrophic factors – BDNF and NGF. The administration of giproline compounds against the background of stress, contributed to the restoration of the studied indicators level, which is most likely due to the presence of antiapoptotic and neuroprotective effects in giprolines due to the inhibition of the caspase-dependent cascade of apoptosis reactions, as well as the induction of the synthesis of neurotrophic factors with the antiapoptotic activity.Conclusion. Thus, the administration of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu under stress conditions, contributes to the restoration of the initiating and effector caspases level, as well as of neurotrophic factors. As a result of the experiment, an anti-apoptotic effect is observed due to the inhibition of the caspase-dependent cascade of reactions, as well as a stress-protective effect is observed due to the restoration of the brain neurotrophic factors level.
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甘脯氨酸对“社会”应激条件下细胞凋亡和神经营养因子水平的影响
本文旨在研究甘脯氨酸神经肽化合物Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank)、Pro-Gly-Pro和Pro-Gly-Pro - leu对实验性“社交”应激大鼠血清中凋亡因子(caspase-3、caspase-8、肿瘤坏死因子)和神经营养因子(神经生长因子和脑神经营养因子)水平的影响。材料和方法。实验研究对象为90只6月龄非线性雄性白种大鼠。根据行为类型,在“社会”应激建模过程中,将所有大鼠分为“攻击者”和“受害者”。本研究分为以下实验组(n=10):对照个体;各组大鼠暴露在压力下20天;各组动物从应激因子暴露第1天开始,以100 μg/kg/天的剂量腹腔注射甘脯氨酸化合物Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank)、Pro-Gly-Pro和Pro-Gly-Pro - leu,疗程20 d。采用酶免疫法测定大鼠血清caspase-3、caspase-8、肿瘤坏死因子、神经生长因子和脑神经营养因子水平,探讨化合物对凋亡因子和神经营养因子水平的影响。研究结果发现,在“社交”应激条件下,大鼠的凋亡过程增加,血清中caspase-3、caspase-8、TNF-α水平升高,神经营养因子- BDNF、NGF浓度降低。应激背景下给予吉脯啉化合物,有助于恢复所研究的指标水平,这很可能是由于吉脯啉通过抑制caspase依赖性的细胞凋亡级联反应,以及诱导具有抗凋亡活性的神经营养因子的合成而具有抗凋亡和神经保护作用。因此,在应激条件下给予甘氨酸神经肽化合物Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank), Pro-Gly-Pro和Pro-Gly-Pro - leu有助于恢复启动和效应半胱天冬酶水平,以及神经营养因子。实验结果表明,由于抑制caspase依赖性级联反应,观察到抗凋亡作用,以及由于恢复脑神经营养因子水平,观察到应激保护作用。
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