Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus
Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus
复制标题
DOI：
10.1016/j.bbr.2017.08.013
复制
发表时间：
2017-09-29
影响因子：
2.7
通讯作者：
Parameshwaran, Kodeeswaran
中科院分区：
文献类型：
--
作者：
Bhakta, Ami;Gavini, Kartheek;Parameshwaran, Kodeeswaran
人类的慢性压力会导致多种不良的精神和神经生物学后果，包括记忆障碍。如果压力的每一次发作都非常令人痛苦，那么这些不良后果可能会更加严重。与急性或短期压力相比，人们对慢性创伤压力对记忆的影响以及海马体分子变化的了解相对较少。海马体是大脑中参与记忆处理的区域。在这里，我们研究了慢性创伤应激对小鼠的影响，方法是将小鼠连续28天暴露于成年Long Evan大鼠，然后分析行为结果和海马区的变化。结果表明，在进行放射臂迷宫测试时，应激小鼠出现了记忆缺陷。然而，慢性创伤应激不会导致焦虑、运动性多动或快感缺乏。应激小鼠海马区IL-1β蛋白表达增加，促肾上腺皮质激素释放激素(CRH)基因表达降低。此外，应激小鼠海马区的乙酰胆碱水平降低。应激小鼠海马区脑源性神经营养因子(BDNF)和神经生长因子(NGF)水平无明显变化。即刻早期基因(Zif268、Arc、C-Fos)以及糖皮质激素和盐皮质激素受体的基因表达也不受慢性应激的影响。这些数据表明，经过一段恢复期后的慢性创伤应激可能会导致恢复力的发展，导致选定的、最脆弱的行为改变和海马体中的分子变化。
Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice in-terleukin-1 beta protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus.