[doi: 10.5505/2017ichc.PP-214]Resveratrol exhibits antidepressant-like behavior in the rat chronic unpredictable mild stress model through reducing serum corticosterone, peripheral inflammation and neuroinflammation and also maintaining hippocampal BDNF levelsYusufhan Yazir1, Selenay Furat Rençber1, Gülçin Gacar2, Ayşegül Aytekin1, Selen Önder2, Tijen Utkan32Stem Cell and Gene Therapies Research and Application Center, Kocaeli University, Kocaeli, Turkey 3Department of Pharmacology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey It is well known that major depressive disorder (MDD) is the most common neuropsychiatric disorders and has been associated with inflammation. Resveratrol (trans 3,5,4-trihydoxystilbene) possesses antidepressant-like effects and antiinflammatory properties. The aim of this study is to examine possible effect of resveratrol on HPA axis function, peripheral inflammation, neuroinflammation and neurogenesis, and associated depressive–like behaviours in rats. Male Wistar albino rats were randomly divided into four groups (n=10): Animals not exposed to CUMS (control), animals exposed to CUMS, and animals treated with resveratrol while exposed to CUMS. Resveratrol was administrated intraperitoneally, 20 mg/kg/day for 12 weeks to the animals being exposed to the CUMS protocol. CUMS and CUMS+resveratrol groups were subjected to different types of stressors. These stressors were randomly applied for 12 weeks. After 12 weeks, Forced swimming test (FST) and the sucrose consumption test (SCT) were used to evaluate the depressive-like behavior of animals. BDNF expression was assessed by immunohistochemically. Plasma corticosterone, proinflammatory (TNF-alpha, IL-1 beta, IL-6) and inflammatory (CRP, MCP-1) cytokines levels and hippocampal proinflammatory cytokines (TNF-alpha, IL-1 beta) levels were assessed with an ELISA kit according to the manufacturer’s instructions. Significant differences were determined using one-way ANOVA followed by Tukey post hoc tests. The immunoreactivity scores were compared by the Kruskal-Wallis test following Dunn’s multiple comparison test. P<0.05 was considered significant. In the FST, CUMS-exposed rats exhibited more immobility than control rats (p<0.05). There were no difference between resveratrol-treated CUMS rats and control rats. In the SCT, CUMS-exposed rats consumed less sucrose solution than controls (p<0.05). However, resveratrol treated stressed rats, the sucrose consumption did not differ significantly from nonstressed controls. Additionally, the results showed a decrease in the hippocampal BDNF immunoreactivity (p<0.05), an increase in plasma corticosterone (p<0.05), TNF-alpha (p<0.05), IL-1 Beta (p<0.05), IL-6 (p<0.05), CRP (p<0.05), MCP-1(p<0.05) levels and an increase in hippocampal TNF-alpha (p<0.05) and IL-1 beta levels (p<0.05). Chronic treatment with resveratrol restored hippocampal BDNF immunoreactivity and reduced plasma and also hippocampal cytokine levels. Our study demonstrated that resveratrol exhibited antidepressant-like behavior in CUMS rats through normalizing serum cortosterone levels, peripheral inflammation and neuroinflammation while also maintaining BDNF levels in the hippocampus. |