Effect Of Jieyuwan On Synaptic Structure Plasticity In Hippocampus And Prefrontal Cortex Of WKY Rats

Objective:Our study was to investigate the mechanism of Jieyuwan on depression-like behavior in WKY rats,and to explore whether its antidepressant effect involves the involvement of synaptic-related proteins in the hippocampus and prefrontal cortex,as well as further observation of changes in synaptic morphological plasticity,and to provides new ideas for the occurrence and treatment of depression.Methods:(1)Adult male Wistar-Kyoto(WKY)rats were endogenous depression animal models.Wistar rats of the same strain were selected as control group.WKY rats were randomly divided into model group,citalopram group(positive control)and Jieyuwan group,administered by intragastric administration for 21 days;(2)Changes in depression-like behaviors of rats in each group were observed by sucrose preference test,forced swimming test and open field test;(3)Tissue immunofluorescence and Western blot were used to detect the expression of PSD95 and SYP in depression-related brain regions,including the hippocampus and prefrontal cortex;(4)Finally,Golgi staining was used to analyze neuronal dendrites variety.Results:1)Behavioral experiments showed that the degree of sucrose preference in WKY rats was significantly decreased(F = 20.252,P < 0.001),and the floating time in forced swimming test increased significantly(F = 43.176,P < 0.001),the total exercise time in the open field test(F = 45.308,P < 0.001)and the time of exploration in the central area was significantly reduced(F = 45.959,P < 0.001);however,after 21 days of treatment with Jieyuwan,the degree of sucrose preference in WKY rats was significantly increased(F = 20.252,P < 0.001),making the floating time of the rats was also increased(F = 43.176,P < 0.001),and increased the total exercise time(F = 45.308,P < 0.001)and central exploration time(F = 45.959,P < 0.001)in the open field test,and there was no statistical difference with the citalopram group.2)Tissue immunofluorescence and Western blot results showed that the expression levels of PSD95 and SYP in the depression-related brain regions of WKY rats were decreased,and the axons of neurons were decreased.The expression of PSD95 protein in hippocampus(F = 11.230,P < 0.001)and prefrontal cortex(F = 34.615,P < 0.001)was significantly decreased,and SYP protein was also reduced in hippocampus(F = 4.301,P < 0.01)and prefrontal cortex(F = 7.827,P < 0.001).After the same treatment with Jieyuwan,the expression levels of PSD95 and SYP in hippocampus and prefrontal cortex increased,and the number of axons increased.The expression of PSD95 protein in hippocampus(F = 11.230,P < 0.001)and prefrontal cortex(F = 34.615,P < 0.001)was significantly increased.SYP protein was in hippocampus(F = 4.301,P < 0.01)and prefrontal cortex(F = 7.827,P < 0.001)also increased,and the expression of related proteins was also increased after citalopram treatment.3)Golgi staining showed that dendritic spine density was significantly decreased in hippocampus(F = 60.598,P < 0.001)and prefrontal cortex(F = 99.075,P < 0.001)of WKY rats,and the number of neurites intersection was decreased in hippocampus(F = 3.821,10.452,9.644,8.09,4.472,5.398,P < 0.05)and prefrontal cortex(F =2.406,5.59,5.526,3.587,2.516,P < 0.05,0.01,0.01,0.01,0.05).The density of the spines of rats treated with Jieyuwan increased in hippocampus(F = 60.598,P < 0.001)and prefrontal cortex(F = 99.075,P < 0.001),and the number of neurites intersection increased significantly in hippocampus(F = 3.821,10.452,9.644,8.09,4.472,5.398,P < 0.01)and prefrontal cortex(F =2.406,5.59,5.526,3.587,P < 0.05,0.01,0.01,0.05).Conclusion:Jieyuwan can effectively improve the depression-like behavior of WKY rats,and verify that PSD95 and SYP in hippocampus and prefrontal cortex participate in antidepressant effects,and can reshape synaptic structure,which also confirms synapses protein and synaptic structure plasticity are involved in the physiological process of depression.