REM sleep deprivation-induced circadian clock gene abnormalities participate in hippocampal-dependent memory impairment by enhancing inflammation in rats undergoing sevoflurane inhalation

Publication date: Available online 16 February 2019

Source: Behavioural Brain Research

Author(s): Jiabao Hou, Qianni Shen, Xing Wan, Bo Zhao, Yang Wu, Zhongyuan Xia

Abstract

Sleep disturbance can result in memory impairment, and both sleep and hippocampal memory formation are maintained by circadian clock genes. Although preoperative sleep deprivation is known to be an independent risk factor for postoperative cognitive dysfunction (POCD) after inhalation anesthesia, the circadian mechanisms involved are currently unclear. To examine this issue, we constructed models of rapid eye movement sleep deprivation (RSD) and POCD after sevoflurane inhalation, to evaluate the circadian mechanisms underlying preoperative sleep deprivation-induced POCD after sevoflurane inhalation. Morris water maze probe test performance revealed that RSD aggravated the hippocampal-dependent memory impairment induced by sevoflurane anesthesia, and the recovery period of memory impairment was prolonged for more than a week by sleep deprivation. Western blot analysis revealed that sleep deprivation inhibited hippocampal Bmal1 and Egr1 expression for more than 7 days after sevoflurane inhalation. Importantly, hippocampal Per2 expression levels were first decreased by sevoflurane inhalation then increased from the third day by sleep deprivation. Sleep deprivation enhanced the expression of hippocampal inflammatory factors IL-1β and IL-6 after sevoflurane inhalation. In addition, sevoflurane inhalation activated the plasma expression of S100β and IL-6, particularly after sleep deprivation. Sleep deprivation aggravated pathogenic impairment of pyramidal neurons and activated astrocytes in CA1 after sevoflurane inhalation. These results suggest that preoperative RSD aggravates hippocampal memory impairment by enhancing neuroinflammatory injuries after sevoflurane inhalation, which is related to hippocampal clock gene abnormalities.

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