Histone Acetylation Regulation in Sleep Deprivation-Induced Spatial Memory Impairment
Histone Acetylation Regulation in Sleep Deprivation-Induced Spatial Memory Impairment
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DOI：
10.1007/s11064-016-1937-6
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发表时间：
2016-09-01
影响因子：
4.4
通讯作者：
Zhang, Zhiqing
中科院分区：
文献类型：
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作者：
Duan, Ruifeng;Liu, Xiaohua;Zhang, Zhiqing
睡眠障碍会对认知和健康产生负面影响。最近的证据表明，染色质重塑通过组蛋白乙酰化调节认知功能。本研究旨在探讨组蛋白乙酰化在睡眠剥夺（SD）所致认知功能损害中的作用。Morris水迷宫实验结果显示，SD大鼠3d后，空间记忆能力明显下降。SD还可以降低组蛋白乙酰化水平，增加组蛋白去乙酰化酶2（HDAC 2）表达，并降低组蛋白乙酰转移酶（CBP）表达。此外，SD可降低脑源性神经营养因子（BDNF）基因启动子中的H3和H4乙酰化水平，从而显著下调BDNF表达并损害关键BDNF信号通路（pCaMKII、pErk2和pCREB）的活性。然而，用HDAC抑制剂阿司他丁A治疗减弱了SD诱导的所有负面作用。因此，BDNF及其组蛋白乙酰化调节可能在SD诱导的空间记忆损伤中起重要作用，而HDAC抑制可能赋予对SD诱导的空间记忆和海马功能损伤的保护作用。
Sleep disorders negatively affect cognition and health. Recent evidence has indicated that chromatin remodeling via histone acetylation regulates cognitive function. This study aimed to investigate the possible roles of histone acetylation in sleep deprivation (SD)-induced cognitive impairment. Results of the Morris water maze test showed that 3 days of SD can cause spatial memory impairment in Wistar rats. SD can also decrease histone acetylation levels, increase histone deacetylase 2 (HDAC2) expression, and decrease histone acetyltransferase (CBP) expression. Furthermore, SD can reduce H3 and H4 acetylation levels in the promoters of the brain-derived neurotrophic factor (Bdnf) gene and thus significantly downregulate BDNF expression and impair the activity of key BDNF signaling pathways (pCaMKII, pErk2, and pCREB). However, treatment with the HDAC inhibitor trichostatin A attenuated all the negative effects induced by SD. Therefore, BDNF and its histone acetylation regulation may play important roles in SD-induced spatial memory impairment, whereas HDAC inhibition possibly confers protection against SD-induced impairment in spatial memory and hippocampal functions.