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.
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This work was supported by grants from the National Natural Science Foundation of China (No. 81302415) and the Tianjin Natural Science Foundation (No. 12JCYBJC15800). The authors declare no conflicts of interest in this manuscript.
Z.Z. conceived the study and designed the experiments. L.W. performed the cognition function detection and analysis. R.D. and X.L. performed the ChIP assay. T.W. and X.G. performed all other experiments. The manuscript was written by R.D. and Z.Z. and reviewed and approved by all authors.
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