Table_1_Long-term environmental enrichment overcomes depression, learning, and memory impairment in elderly CD-1 mice with maternal sleep deprivation exposure.DOCX

Early-life stress disrupts central nervous system development and increases the risk of neuropsychiatric disorder in offspring based on rodent studies. Maternal sleep deprivation (MSD) in rodents has also been associated with depression and cognitive decline in adult offspring. However, it is not known whether these issues persist into old age. Environmental enrichment is a non-pharmacological intervention with proven benefits in improving depression and cognitive impairment; however, it is unclear whether these benefits hold for aging mice following MSD exposure. The aim of this study was to explore the effects of MSD on depression and cognition in elderly offspring CD-1 mice and to determine whether long-term environmental enrichment could alleviate these effects by improving neuroinflammation and synaptic plasticity. The offspring mice subjected to MSD were randomly assigned to either a standard environment or an enriched environment. At 18 months of age, the forced swimming and tail suspension tests were used to evaluated depression-like behaviors, and the Morris water maze test was used to evaluate cognitive function. The expression levels of hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins were also measured. MSD increased depression-like behaviors and impaired cognition function in aging CD-1 offspring mice. These effects were accompanied by upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-α expression, and downregulated brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin expression in the hippocampus. All of these changes were reversed by long-term exposure to an enriched environment. These findings suggest that MSD exerts long-term effects on the behaviors of offspring in mice, leading to depression and cognitive impairment in older age. Importantly, long-term environmental enrichment could counteract the behavior difficulties induced by MSD through improving hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins.

早期生活压力破坏中枢神经系统发育并增加后代患神经精神疾病的风险，此结论基于啮齿动物研究。母鼠睡眠剥夺（MSD）亦与成年后代抑郁和认知能力下降相关。然而，这些问题是否持续至老年期尚不明确。环境富集作为一种非药物治疗手段，已被证实有助于改善抑郁和认知障碍；然而，这些益处是否在MSD暴露后的老龄小鼠中得以维持尚不清楚。本研究旨在探讨MSD对老龄后代CD-1小鼠抑郁和认知能力的影响，并确定长期环境富集是否通过改善神经炎症和突触可塑性来缓解这些影响。遭受MSD的幼鼠被随机分配至标准环境或富集环境。在18个月大时，强迫游泳和悬尾测试被用于评估抑郁样行为，而Morris水迷宫测试则用于评估认知功能。海马区促炎细胞因子和突触可塑性相关蛋白的表达水平也被测量。MSD增加了老龄CD-1后代小鼠的抑郁样行为和认知功能障碍。这些效应伴随着海马区白介素（IL）-1β、IL-6和肿瘤坏死因子-α表达的上调，以及脑源性神经营养因子、酪氨酸激酶受体B、突触密度-95和突触素表达的降低。所有这些变化均可在长期接触富集环境后逆转。这些发现表明，MSD对小鼠后代行为产生长期影响，导致老年期抑郁和认知障碍。值得注意的是，长期环境富集可以通过改善海马区促炎细胞因子和突触可塑性相关蛋白来抵消MSD诱导的行为困难。