Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro

•Resveratrol prevents cognitive impairment induced by chronic unpredictable mild stress.•Resveratrol treatment increases Sirt1, p-CREB, CREB, BDNF expression and decreases miR134 levels in hippocampus.•The effects of resveratrol are mediated by activating Sirt1/miR134 pathway. Chronic unpredictable...

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Veröffentlicht in:Behavioural brain research 2018-09, Vol.349, p.1-7
Hauptverfasser: Shen, Jun, Xu, Linling, Qu, Chujie, Sun, Huimin, Zhang, Junjian
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Sprache:eng
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Zusammenfassung:•Resveratrol prevents cognitive impairment induced by chronic unpredictable mild stress.•Resveratrol treatment increases Sirt1, p-CREB, CREB, BDNF expression and decreases miR134 levels in hippocampus.•The effects of resveratrol are mediated by activating Sirt1/miR134 pathway. Chronic unpredictable mild stress (CUMS) leads to neuropsychiatric disorders, such as depression, anxiety and cognitive impairment. Resveratrol is a natural polyphenol existed in polygonum cuspidatum and has been demonstrated to be a potent activator of Sirtuin 1 (Sirt1). Previous studies reported that resveratrol treatment ameliorated CUMS-induced depressive-like behavior and cognitive deficits through upregulating cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) expression. However, the upstream signalling pathway mediating CREB/BDNF expression and then exerting a protective role on cognitive function remains unclear. The present study aims to investigate the possible mechanism of resveratrol on CUMS-induced cognitive deficits. Male Sprague Dawley rats were adminstrated resveratrol (40 and 80 mg/kg) every day for 4 consecutive weeks before exposure to CUMS procedure. Morris Water Maze test was used to appraise spatial learing and memory of rats. Sirt1/miR-134 signalling pathway and CREB/BDNF expression in hippocampus of rats were measured. We also explored Sirt1/miR-134 signalling pathway and CREB/BDNF expression in primary cultured hippocampus neurons with resveratrol (25, 50 and 100 μmol/L) treatment. We found that resveratrol treatment prevented spatial learing and memory impairment induced by CUMS. Meanwhile the potential mechanism of resveratrol was associated with increased levels of Sirt1, CREB phosphorylation (p-CREB), CREB, BDNF and decreased levels of miR-134 in vivo and in vitro. In conclusion, our study showed that the neuroprotective effect of resveratrol on CUMS-induced cognitive impairment may rely on activating Sirt1/miR-134 pathway and then upregulating its downstream CREB/BDNF expression in hippocampus.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2018.04.050