Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice
Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice
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DOI：
10.1016/j.bbr.2016.09.011
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发表时间：
2017-01-01
影响因子：
2.7
通讯作者：
Wang Shao-Hui
中科院分区：
文献类型：
--
作者：
Fan Jianhua;Wei Wei;Wang Shao-Hui
众所周知，社会挫败压力会导致抑郁行为和认知障碍。然而，只有一小部分压力暴露的个体受到影响的分子机制尚不清楚。本研究将30只3周龄雄性C57BL/6小鼠暴露于30天的社会失败应激中，然后通过社会调查确定易感(社会回避)和不敏感(社会互动)的小鼠。在最后一次失败的24小时后，分别对不同组的小鼠进行了蔗糖偏爱、开阔场地、高架正迷宫和Morris水迷宫行为测试。此外，还检测了海马区记忆相关蛋白的水平，包括突触后密度95(PSD95)、突触后密度93(PSD93)和蛋白激酶A(PKA)。PSD95、PSD93和PICA水平在易感小鼠中显著降低。我们还发现，这些蛋白的上游调控因子磷酸化cAMP反应元件结合蛋白(CREB)在社会失败后降低，而组蛋白脱乙酰基酶6(HDAC6)的水平显著升高。这些数据表明，记忆相关蛋白和磷酸化的CREB可能在记忆障碍和对慢性应激的行为反应中发挥重要作用。(C)2016爱思唯尔B.V.保留所有权利。
It is well known that social defeat stress can induce depressive behaviours and cognitive impairment. However, the molecular mechanism by which only a minority of stress-exposed individuals are affected is not clear. In this study, thirty 3-week-old male c57BL/6 mice were exposed to 30 days of social defeat stress, following which susceptible (socially avoidant) and unsusceptible (socially interactive) mice were identified using social investigation. Twenty-four hours after the last episode of defeat, separate groups of mice were tested in the sucrose preference, open field, elevated plus-maze and Morris water maze behavioural assays. Also, the levels of memory-associated proteins in the hippocampus were examined, including postsynaptic density 95 (PSD95), postsynaptic density 93 (PSD93), and Protein kinase A (PKA). The levels of PSD95, PSD93, and PICA were significantly lower in susceptible mice. We also found that the upstream regulatory factor of these proteins, phosphorylated Camp-Responsive Element-Binding Protein (CREB), was reduced after social defeat in the susceptible group only, while the level of histone deacetylase 6 (HDAC6) was significantly elevated. These data suggest that memory-associated proteins and phosphorylated CREB may play important roles in memory impairment and behavioural responses to chronic stress. (C) 2016 Elsevier B.V. All rights reserved.