Effects of resveratrol on cognitive dysfunction and the expression of parvalbumin in depression model mice

Abstract

Objective To examine the antidepressant effects of resveratrol (RSV), and its possible mechanism specialized on improving cognitive function. Methods Thirty-two C57BL/6J mice were randomly divided into four groups: Control, Model, Model+ RSV and Model+ NA+ RSV groups.The mice were subjected corticosterone (20 mg/(kg·d)) intraperitoneal injection for 21 consecutive days except the control mice.From the 22nd to 42nd day, the mice in different groups received further treatment with vehicle/ RSV (400 mg/(kg·d), op)/ NA (100 mg/(kg·d), ip)+ RSV (400 mg/(kg·d), op) .The sugar preference test, novel object recognition test, novel location recognition test and water maze test were applied to evaluate the cognitive effects of RSV on mice.Subsequently, the silence information regulation factor 1(SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α), parvalbumin(PV) transcription and translation level were evaluated by RT-PCR and Western blotting. Results The sugar preference test showed that the depression model mediated by CORT injection was successfully established(F(1, 30)=6, P=0.038). In in the novel object learning test, resveratrol significantly increased the proration on the frequency((-0.20±0.37) vs ( 0.16±0.29) )and duration((0.10±0.45) vs ( 0.62±0.29)) and decreased the proration on the distance((0.09±0.36) vs (0.55±0.27)). In the water maze test, resveratrol reduced the time((41±9 )s; (26±8)s) and distance ((295±70)cm; (224±43)cm)to find the platform.All the results were accompanied with the increased expression of protein SIRT1 (F(3, 29)=15.60, P<0.01), PGC-1α (F(3, 29)=7.51, P=0.0006) and PV (F(3, 29)=17.87, P=0.0004). While pretreatment with nicotinamide, resveratrol could not rescue the cognitive impairment and could not reverse the iecreased expression level of protein SIRT1, PGC-1α and PV. Conclusion Resveratrol can reverse the cognitive dysfunction of depressant mice, which may be achieved by activating the SIRT1/ PGC-1α signaling pathway and increasing the transcription and protein expression of PV. Key words: Resveratrol; Depression; Cognition; SIRT1; PGC-1α; Parvalbumin; Mice