Histone Acetylation Regulation in Sleep Deprivation-Induced Spatial Memory Impairment

• Published in: Neurochemical research 2016-09, Vol.41 (9), p.2223-2232
• Main Authors: Duan, Ruifeng, Liu, Xiaohua, Wang, Tianhui, Wu, Lei, Gao, Xiujie, Zhang, Zhiqing
• Format: Article
• Language: English
• Subjects: Acetylation; Animal behavior; Animal memory; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cell Biology; Chromatin remodeling; Cognition; Cognitive ability; Epigenesis, Genetic - physiology; Gene expression; HDAC2 protein; Hippocampus; Hippocampus - metabolism; Histone acetyltransferase; Histone deacetylase; Histone Deacetylase 2 - metabolism; Histones - metabolism; Impairment; Male; Memory; Memory Disorders - etiology; Memory Disorders - metabolism; Memory tasks; Neurochemistry; Neurology; Neurosciences; Original Paper; Protein Processing, Post-Translational - genetics; Rats, Wistar; Sleep; Sleep deprivation; Sleep Deprivation - complications; Sleep Deprivation - metabolism; Sleep disorders; Spatial analysis; Spatial memory; Spatial Memory - physiology; Trichostatin A
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-016-1937-6

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.