Hippocampal microRNA-191a-5p Regulates BDNF Expression and Shows Correlation with Cognitive Impairment Induced by Paradoxical Sleep Deprivation

The aim of this study was to investigate the effect of paradoxical sleep deprivation (PSD) on the BDNFrelated miRNA expression in ovariectomized (OVX) rats. The animals were randomly divided into eight groups (control, PSD, wide platform, sham surgery, anti-miR-191, anti-miR-191/PSD, scrambled and PSD in intact). Bilateral-ovariectomy was performed one month before the experiment in the OVX rats. For the induction of 72 h of PSD, the multiple platform method was applied. The Morris water maze (MWM) test was carried out 30 min after PSD to test spatial learning and memory. Finally, the rats were euthanized 24 h after the last experiment. We quantified miR10a- 5P, miR-10b-5P, miR-125a-3p, miR-155-5p, miR-191a-5p, BDNF and TMOD-2 level using real-time PCR. BNDF protein was also measured by Western blotting. Hippocampal miR-191a and miR-155 were significantly up-regulated (P .01) and BDNF down-regulated (P.05) in the PSD group. PSD rats with up-regulated miR-191a swam longer distance and spent more time to find a hidden platform (positive correlation) and showed the lowest percentage of time and distance in the target quadrant (negative correlation). The negative correlation between miR-191a and BDNF levels in the PSD condition provided more evidence for the role of miR-191a in cognitive function. Intracerebroventricular (ICV) injection of anti-miR-191a improved the down-regulation of BDNF and attenuated PSD-induced cognitive impairment. Hippocampal BDNF is probably one of the targets of miR-191a in sleep-deprived OVX rats. Our results suggest that miR-191a may be increased in the sleep-deprived OVX rats to regulate BDNF levels. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.