Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, 238000 Anhui, China.
Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601 Anhui, China.
Neural Plast. 2022 May 6;2022:1483101. doi: 10.1155/2022/1483101. eCollection 2022.
A mounting body of evidence suggests that prenatal inflammation may enhance the rate of age-associated cognitive decline and may involve aberrant amounts of synaptic proteins in the hippocampus, including synaptotagmin-1 (Syt1) and activity-regulated cytoskeleton-associated protein (Arc). However, little is known about the specific impact of adolescent environmental enrichment (EE) on age-associated cognitive decline and the changes in synaptic proteins caused by prenatal inflammation. In this study, CD-1 mice in late pregnancy were given intraperitoneal doses of lipopolysaccharide (LPS, 50 g/kg) or normal saline. Offspring arising from LPS dams were divided into a LPS group and a LPS plus EE (LPS-E) group. The LPS-E mice were exposed to EE from 2 months of age until the end of the experiment (3 or 15 months old). The Morris water maze (MWM) was used to assess the spatial learning and memory capacities of experimental mice, while western blotting and RNA-scope were used to determine the expression levels of Arc and Syt1 in the hippocampus at the protein and mRNA levels, respectively. Analysis revealed that at 15 months of age, the control mice experienced a reduction in cognitive ability and elevated expression levels of and genes when compared to control mice at 3 months of age. The LPS-E group exhibited better cognition and lower protein and mRNA levels of Arc and Syt1 than mice in the LPS group of the same age. However, the enriched environment mitigated but did not counteract, the effects of prenatal inflammation on cognitive and synaptic proteins when tested at either 3 or 15 months of age. Our findings revealed that long-term environmental enrichment improved the expression levels of synaptic proteins in CD-1 mice and that this effect was linked to the dysfunctional cognition caused by prenatal inflammation; this process may also be involved in the reduction of hippocampal and gene expression.
越来越多的证据表明，产前炎症可能会加速与年龄相关的认知能力下降，并且可能涉及海马突触蛋白的异常，包括突触结合蛋白-1（Syt1）和活性调节细胞骨架相关蛋白（Arc）。然而，关于青春期环境富集（EE）对与年龄相关的认知能力下降的具体影响以及产前炎症引起的突触蛋白变化知之甚少。在这项研究中，妊娠晚期的 CD-1 小鼠接受腹腔内注射脂多糖（LPS，50μg/kg）或生理盐水。来自 LPS 母鼠的后代分为 LPS 组和 LPS 加 EE（LPS-E）组。LPS-E 组从 2 个月大开始暴露于 EE，直到实验结束（3 或 15 个月大）。Morris 水迷宫（MWM）用于评估实验小鼠的空间学习和记忆能力，而 Western blot 和 RNA-scope 分别用于确定海马中 Arc 和 Syt1 的蛋白和 mRNA 水平表达。分析表明，在 15 个月大时，与 3 个月大的对照小鼠相比，对照组的认知能力下降，Arc 和 Syt1 的基因表达升高。LPS-E 组的认知能力优于同年龄的 LPS 组，且 Arc 和 Syt1 的蛋白和 mRNA 水平较低。然而，丰富的环境减轻了但并没有抵消产前炎症对认知和突触蛋白的影响，无论是在 3 个月还是 15 个月大时进行测试。我们的研究结果表明，长期环境富集改善了 CD-1 小鼠突触蛋白的表达水平，这种作用与产前炎症引起的认知功能障碍有关；这一过程可能还涉及海马中 和 基因表达的降低。
