Effect of naringin on despair behavior and neuroprotective mechanisms in mouse model of menopausal depression

Objective:To explore the effect of naringin on hippocampus estrogen receptor and neuronal cell apoptosis in a mouse model of menopausal depression.Methods:The menopausal depression model was replicated by bilateral ovariectomy(OVX)combined with chronic unpredictable mild stimulation(CUMS),54 female Kunming mice were randomly divided into Blank group,Model group(OVX+CUMS group),Sham operation group(SHAM group),Estradiol group(E2 group 20.090 mg∙Kg-1∙d-1),Naringin group(100 mg∙Kg-1∙d-1),Naringin+ICI182780 group(100 mg∙Kg-1∙d-1+0.075 mg∙Kg-1∙d-1),each group of 9 mice were administered for 21 consecutive days.The depression-like behaviour changes of each group of mice were observed by tail suspension and forced swimming experiments;The morphological changes of hippocampal neurons were observed by HE staining;Immunohistochemical method was used to detect the expression of ERαand ERβpositive cells in the hippocampus of mice;The expression of ERβ,GluR2,CAMK栻,NMDAR1,Bad,Bcl-2 and Caspase3 proteins in the hippocampus of the mice was detected by western blot.Results:Compared with the Blank group,the immobility time of the mice in the OVX+CUMS group was significantly increased(P<0.01),mice hippocampal neurons with a sparsely organized cell arrangement,nuclear fixation,the expressions of ERβ,GluR2,and Bcl-2 were decreased(P<0.01,P<0.001),and the expressions of NMDAR1,CAMK栻,Bad,and Caspase3 were increased(P<0.05,P<0.01);Compared with the OVX+CUMS group,the immobility time of the mice in the SHAM group,E2 group and Naringin group was significantly reduced(P<0.01),mice hippocampal neuronal cells are relatively intact and tightly packed,the expressions of ERβ,GluR2 and Bcl-2 were increased(P<0.01,P<0.05),and the expressions of NMDAR1,CAMK栻,Bad and Caspase3 were decreased(P<0.05,P<0.01);Compared with the Naringin group,the quiescent time of the mice in the Naringin+ICI182780 group was increased(P<0.05),the smaller cell body of mouse hippocampal neurons,the expressions of ERβ,GluR2,and Bcl-2 were decreased(P<0.01,P>0.05,P<0.05),and the expressions of NMDAR1,CAMK栻,Bad,and Caspase3 were increased(P<0.01,P<0.05).Conclusions:Naringin may reduce neuronal cell excitotoxicity caused by glutamate receptor activation,reduce neuronal cell apoptosis and improve depression-like behavior by activating ERβreceptors in the hippocampus in a mouse model of menopause depression.