Abstract

Early-life stress is a risk factor for the development of behavioral and cognitive disorders in humans and animals. Such stressful situations include social isolation in early postnatal ontogenesis. Behavioral and cognitive impairments associated with neuroplastic changes in brain structures. We have found that after ten weeks of social isolation, male Wistar rats show behavioral abnormalities and cognitive deficit, accompanied by an increase in the relative expression of gene encoding serine protease prolyl endopeptidase (PREP, EC 3.4.21.26) in the brain frontal cortex. The present study aimed to assess synaptophysin (SYP), brain-derived neurotrophic factor precursor (proBDNF), and PREP expression using Western blot in the brain structures – the hippocampus, frontal cortex, and striatum of the rats subjected to prolonged social isolation compared with group-housed animals. Twenty Wistar rats were used for this study (10 males and 10 females). Experimental animals (5 males and 5 females) were kept one per cage for nine months, starting from the age of one month. Ten-month-old socially isolated rats showed memory deficit in passive avoidance paradigm and Morris Water Maze and reactivity to novelty reduction. We used monoclonal antibodies for the Western blot analysis of the expression of SYP, proBDNF, and PREP in the rat brain structures. Social isolation caused a proBDNF expression reduction in the frontal cortex in females and a reduction in PREP expression in the striatum in males. These data suppose that neurotrophic factors and PREP are involved in the mechanisms of behavioral and cognitive impairments observed in the rats subjected to prolonged social isolation with an early life onset.

中文翻译：

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长期社会隔离降低了大鼠脑中 BDNF 前体和脯氨酰内肽酶的表达

摘要

早期生活压力是人类和动物发生行为和认知障碍的危险因素。这种压力情况包括出生后早期个体发育中的社会孤立。与大脑结构的神经可塑性变化相关的行为和认知障碍。我们发现，在社会隔离十周后，雄性 Wistar 大鼠表现出行为异常和认知缺陷，伴随着大脑额叶皮层中编码丝氨酸蛋白酶脯氨酰内肽酶（PREP，EC 3.4.21.26）的基因的相对表达增加。本研究旨在评估突触素 (SYP)、脑源性神经营养因子前体 (proBDNF) 和 PREP 在大脑结构中的表达——海马、额叶皮层、与群养动物相比，长期社会隔离的大鼠的纹状体和纹状体。本研究使用 20 只 Wistar 大鼠（10 只雄性和 10 只雌性）。实验动物(5雄5雌)从1个月大开始，每笼饲养1只，共饲养9个月。10 个月大的社会隔离大鼠在被动回避范式和莫里斯水迷宫中表现出记忆缺陷，并且对新奇减少的反应性。我们使用单克隆抗体对大鼠脑结构中 SYP、proBDNF 和 PREP 的表达进行蛋白质印迹分析。社会隔离导致女性额叶皮层 proBDNF 表达减少，男性纹状体 PREP 表达减少。