Resveratrol prevents impaired cognition induced by chronic unpredictable mild stress in rats

Depression is one of the most common neuropsychiatric disorders and has been associated with impaired cognition, as well as causing neuroendocrine systems and brain proteins alterations. Resveratrol is a natural polyphenol enriched in polygonum cuspidatum and has diverse biological activities, including potent antidepressantlike effects. The aim of this study was to determine whether resveratrol administration influences chronic unpredictable mild stress (CUMS)-induced cognitive deficits and explores underlying mechanisms. The results showed that CUMS (5 weeks) was effective in producing cognitive deficits in rats as indicated by Morris water maze and novel object recognition task. Additionally, CUMS exposure significantly elevated serumcorticosterone levels and decreased BDNF levels in the prefrontal cortex (PFC) and hippocampus, accompanied by decreased phosphorylation of extracellular signal-regulated kinase (pERK) and cAMP response element-binding protein (pCREB). Chronic administration of resveratrol (80 mg/kg, i.p., 5 weeks) significantly prevented all these CUMS-induced behavioral and biochemical alterations. In conclusion, our study shows that resveratrol may be an effective therapeutic agent for cognitive disturbances aswas seenwithin the stressmodel and its neuroprotective effectwas mediated in part by normalizing serumcorticosterone levels, up-regulating of the BDNF, pCREB and pERK levels. (C) 2013 Elsevier Inc. All rights reserved.