Curcumin Promotes Post-stroke Depression By Activating The CAMP/PKA Pathway To Inhibit The Inflammatory

Objective: The purpose of this study was to investigate the mechanism of curcumin in the treatment of post-stroke depression(PSD),and to determine whether curcumin can improve the PSD by activating the cAMP/PKA pathway to inhibit the inflammatory response.Methods: 1.Middle cerebral artery occlusion(MCAO)was used to construct the rat model of stroke.Body weight was used to assess the growth status of rats,behavioral tests(Sucrose preference test,Forced swimming test,Open-field test)were used to evaluate the depressive behavior of rats,and than the rat model of PSD was screened.2.Experimental rats were intraperitoneally injected with curcumin.Body weight was used to assess the growth status of rats.Behavioral tests assessed the improvement of depressive behavior in rats.Histopathological changes of hippocampal neurons in rats were observed by HE staining.Immunohistochemistry and WB were used to detect the expression of cAMP,CREB,and BDNF in the rat hippocampus.ELISA was used to determine the content of TNF-? and IL-1? in rat hippocampus.3.The injection of H-89 into the lateral ventricle of rats blocked the cAMP / PKA pathway.Body weight was used to evaluate the growth status of the rats.Behavioral test was used to evaluate the depression behavior of the rats.Histopathological changes of hippocampal neurons in rats were observed by HE staining.The content of TNF-? and IL-1? in rat hippocampus was determined by ELISA.4.Injecting lipopolysaccharide(LPS)into the lateral ventricle of rats to induces overexpression of inflammatory factors in the hippocampus of rats.Body weight was used to evaluate the growth status of the rats,and the behavioral test was used to evaluate the depression behavior of the rats.HE staining was used to observe the morphology of the hippocampus.Results: 1.In the 4th week after MCAO,the rats showed stagnation of weight gain,loss of pleasure,decreased activity and hopelessness,indicating that the PSD rats were successfully modeled.Compared with the control group,the hippocampal neurons of PSD rats were significantly damaged,the expression of cAMP,CREB,and BDNF in the hippocampus decreased significantly,while the content of TNF-? and IL-1? increased significantly.2.The PSD rats which intervened by Cur increased their body weight.Their depressive symptoms improved significantly,the damage of hippocampal neurons was improved,the content of cAMP,CREB and BDNF in hippocampus increased,and the content of TNF-? and IL-1? decreased.3.Cur respectively treated two groups of PSD rats with normal cAMP / PKA pathway and blocked cAMP / PKA pathway.There were significant differences in body weight,depressive symptoms,hippocampal tissue morphology,and hippocampal tissue inflammation levels between the two groups.4.LPS induces PSD rats,and the content of TNF-? and IL-1? in rat hippocampus is significantly increased.Cur treated the two groups of PSD rats with and without LPS induction respectively.There were significant differences in body weight,depressive symptoms and hippocampal morphology between the two groups.Conclusion: Cur can inhibit the inflammatory response by activating the cAMP/PKA pathway and play an anti-PSD role in the rat model.