The Cerebralcare Granule Ameliorate Emotion Of MicroRNA-30e Hippocampus Overexpression Rats Base On RS-fMRI And Molecular Alterations

Objective: The therapeutic effects of Cerebralcare Granule(CG)on Micro RNA-30 e overexpressed rats have been investigated based on previous study in which results demonstrated mi R-30 e overexpression induced sign of anxiety.To further investigate the effects of CG on rats emotion,a multiscale study was employed including behavioral tests,Resting-state f MRI,and immunohistochemistry,and the correlations between these results were also been studied.Methods: Forty male adult SD rats were randomly divided into Control group,Sham group,Model group,CG high group,and CG low group(n=8 each).In these groups,Micro RNA-30 e was carried by lentivirus vectors and transfected each hippocampus CA1 regions by a stereotaxic device in Model,CG high and CG low group,while mi R-30 e lentivirus vectors were replaced by blank vectors in Sham group.After two weeks of transfection,CG water solutions were injected 10ml(50mg/ml)in CG high group and 10ml(25mg/ml)in CG high group through intragastric administration.At same time,same amount of saline were gave in Control,Sham and Model groups.After two week administration,all rats were received behavioral tests,Resting-State f MRI(RS-f MRI),and immunohistochemistry.Results:In open field test,the central area distance was significantly decreased in Model group compared with Control(P<0.05).After CG administration,CG high group showed significant increased central area distance(P<0.05),but CG low group did not have any change.In elevated plus maze,the percent of open arm time was significantly decreased in Model group compared with Control(P<0.01).After CG administration,CG high group showed significant increased performance(P<0.01),but CG low group still did not have any change.The RS-f MRI data showed that the hippocampus Re Ho of Model group was significantly decreased compared with Control(FDR,P<0.05)and CG high group showed increased Re Ho after drug administration(FDR,P<0.05).The functional connectivity between hippocampus and frontal area,anterior cingulate were significantly decreased in Model group compared with Control(FDR,P<0.05),and CG high group showed increased sign of the functional connectivity(FDR,P<0.05).Additionally,CG low did not have significant Re Ho and FC changes compared with Model group.The immunohistochemistry assay of hippocampus showed downregulated Bcl-2 and UBC9 in Model group(P<0.01)and upregulation in CG high group(P<0.01).And expression level of Bcl-2 and UBC9 negatively correlated to strength of functional connectivity between hippocampus and frontal area,anterior cingulate areas.Conclusion: CG can ameliorate the anxiety of rats caused by hippocampus mi R-30 e overexpression.The therapeutic effects may achieved by hippocampus regional function improvement,anti-apoptosis and enhancement of functional connectivity between hippocampus and frontal area,anterior cingulate areas.