Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice
Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice
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怀孕期间的炎症损伤加速了 CD-1 小鼠与年龄相关的行为和神经生化变化
DOI：
10.1007/s11357-016-9920-3
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
Yan, Wen-Wen
中科院分区：
文献类型：
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作者：
Li, Xue-Yan;Wang, Fang;Yan, Wen-Wen
数据显示，妊娠期间的炎症会对后代产生长期影响，例如增加动物成年认知能力下降的风险。然而，目前尚不清楚妊娠期炎症是否会影响母亲自身在衰老过程中的神经行为和神经生化结果。在这项研究中，妊娠CD-1小鼠在妊娠第15-17天每天腹腔内接受两种剂量（分别为25和50 g/kg）的脂多糖（LPS）或生理盐水。在15个月大时，采用一系列行为任务来评估他们的物种典型行为，感觉运动能力，焦虑水平以及空间学习和记忆能力。免疫组化法初步检测β淀粉样蛋白、磷酸化tau蛋白、突触前蛋白synaptotagmin-1和syntaxin-1、胶质细胞酸性蛋白（GFAP）、组蛋白4（H4 K8 ac）乙酰化等神经生化指标。行为结果表明，妊娠期间暴露于LPS加剧了15个月大的CD-1小鼠筑巢能力、感觉运动和空间学习记忆能力的下降，并增加了它们的焦虑水平。神经生化结果表明，妊娠期LPS暴露也加剧了与年龄相关的海马变化，包括淀粉样蛋白-β42、磷酸化tau蛋白、突触结合蛋白-1和GFAP的增加，以及突触融合蛋白-1和H4 K8 ac的减少。本研究结果提示妊娠期炎症损伤可能是阿尔茨海默病发生的重要危险因素，H4 K8乙酰化可能在其发病机制中起重要作用。这项研究为改善支持健康发展和成功老龄化的策略提供了一个视角。
Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15–17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-β, phosphorylated tau, presynaptic proteins synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice’s abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-β42, phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer’s disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging.