Zhang Zhe-Zhe, Zhuang Zhan-Qiang, Sun Shi-Yu, Ge He-Hua, Wu Yong-Fang, Cao Lei, Xia Lan, Yang Qi-Gang, Wang Fang, Chen Gui-Hai
Department of Neurology or Department of Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, China.
Front Aging Neurosci. 2020 Jul 6;12:157. doi: 10.3389/fnagi.2020.00157. eCollection 2020.
Age-associated impairment of spatial learning and memory (AISLM) presents substantial challenges to our health and society. Increasing evidence has indicated that embryonic exposure to inflammation accelerates the AISLM, and this can be attributable, at least partly, to changed synaptic plasticity associated with the activities of various proteins. However, it is still uncertain whether social psychological factors affect this AISLM and/or the expression of synaptic protein-associated genes. Synaptotagmin-1 (Syt1) and activity-regulated cytoskeleton-associated protein (Arc) are two synaptic proteins closely related to cognitive functions. In this study, pregnant CD-1 mice received daily intraperitoneal injections of lipopolysaccharide (LPS) (50 μg/kg) or normal saline at days 15-17 of gestation, and half of the offspring of each group were then subjected to stress for 28 days in adolescence. The Morris water maze (MWM) test was used to separately evaluate spatial learning and memory at 3 and 15 months of age, while western blotting and RNAscope assays were used to measure the protein and mRNA levels of Arc and Syt1 in the hippocampus. The results showed that, at 15 months of age, control mice had worse cognitive ability and higher protein and mRNA levels of Arc and Syt1 than their younger counterparts. Embryonic exposure to inflammation or exposure to stress in adolescence aggravated the AISLM, as well as the age-related increase in Arc and Syt1 expression. Moreover, the hippocampal protein and mRNA levels of Arc and Syt1 were significantly correlated with the performance in the learning and memory periods of the MWM test, especially in the mice that had suffered adverse insults in early life. Our findings indicated that prenatal exposure to inflammation or stress exposure in adolescence exacerbated the AISLM and age-related upregulation of Arc and Syt1 expression, and these effects were linked to cognitive impairments in CD-1 mice exposed to adverse factors in early life.
年龄相关的空间学习和记忆障碍（AISLM）给我们的健康和社会带来了巨大挑战。越来越多的证据表明，胚胎期暴露于炎症会加速AISLM，这至少可以至少部分归因于与各种蛋白质活性相关的突触可塑性变化。然而，社会心理因素是否会影响这种AISLM和/或突触蛋白相关基因的表达仍不确定。突触结合蛋白-1（Syt1）和活性调节细胞骨架相关蛋白（Arc）是两种与认知功能密切相关的突触蛋白。在本研究中，怀孕的CD-1小鼠在妊娠第15至17天每天腹腔注射脂多糖（LPS）（50μg/kg）或生理盐水，然后每组的一半后代在青春期接受28天的应激。使用莫里斯水迷宫（MWM）试验分别评估3个月和15个月大时的空间学习和记忆，同时使用蛋白质印迹和RNAscope分析来测量海马中Arc和Syt1的蛋白质和mRNA水平。结果表明，在15个月大时，对照小鼠的认知能力比年轻小鼠差，Arc和Syt1的蛋白质和mRNA水平更高。胚胎期暴露于炎症或青春期暴露于应激会加重AISLM，以及与年龄相关的Arc和Syt1表达增加。此外，Arc和Syt1的海马蛋白质和mRNA水平与MWM试验学习和记忆期的表现显著相关，尤其是在早年遭受不良损伤的小鼠中。我们的研究结果表明，产前暴露于炎症或青春期暴露于应激会加剧AISLM以及与年龄相关的Arc和Syt1表达上调，这些影响与早年暴露于不利因素的CD-1小鼠的认知障碍有关。
