The Study Of Estrogen Regulation On Perimenopause-related Depression

Objective:In order to provide further evidence for perimenopausal depression treatment,perimenopausal depression patients and mice model were used to inquire the anti-depression effects of estrogen and explore its possible mechanism in terms of behavioral pharmacology and ELISA.Perimenopausal depression mice model was established by bilateral ovariectomy（OVX）combined with chronic unpredictable mild stress（CUMS）.Methods:Clinical research:33 patients diagnosed with perimenopausal depressive disorder by ICD-10 were used as the depression group,and 32 healthy perimenopausal women were used as the control group.General clinical data were collected.The serum concentration of estradiol（E₂）,5-HT,and BDNF were tested by ELISA.Animal research:50 ICR mice were randomly assigned into 5 groups（n=10）,including sham operation group（SHAM）,model group（OVX+CUMS）,estrogen group（OVX+CUMS+E₂）,estrogen+estrogen antagonist group（OVX+CUMS+E₂+ICI）,and estrogen antagonist group（OVX+CUMS+ICI）.Behavioral pharmacological examinations were conducted.The expression of 5-HT,NE and BDNF in serum and brain tissues of mice were detected by ELISA.Results:1.Compared with control group,E₂,5-HT,and BDNF serum concentration decreased significantly in depressive group（P<0.01）.2.Compared with sham group,TST and FST prolonged significantly in OVX+CUMS group（P<0.01）;Compared with OVX+CUMS group,TST and FST shortened significantly in OVX+CUMS+E₂group（P<0.01）.3.Compared with sham group,the serum concentration of 5-HT,BDNF decreased significantly in OVX+CUMS group（P<0.01）;Compared with OVX+CUMS group,the serum concentration of 5-HT,BDNF elevated significantly in OVX+CUMS+E₂group（P<0.01）;Compared with OVX+CUMS+E₂group,the serum concentration of 5-HT,BDNF decreased significantly in OVX+CUMS+E₂+ICI group（P<0.01）.4.Compared with sham group,the level of 5-HT,NE,and BDNF in the prefrontal cortex decreased significantly in OVX+CUMS group（P<0.01）;Compared with OVX+CUMS group,the level of 5-HT,NE,and BDNF in the prefrontal cortex increased significantly in OVX+CUMS+E₂group was（P<0.01）;Compared with OVX+CUMS+E₂group,the level of 5-HT,NE,and BDNF in the prefrontal cortex decreased significantly in OVX+CUMS+E₂+ICI group（P<0.01）.5.Compared with sham group,the level of 5-HT,NE,and BDNF in the hippocampus decreased significantly in OVX+CUMS group（P<0.01）;Compared with OVX+CUMS group,the level of 5-HT,NE,and BDNF in the hippocampus increased significantly in OVX+CUMS+E₂group（P<0.01）;Compared with OVX+CUMS+E₂group,the level of 5-HT and BDNF in the hippocampus decreased significantly in OVX+CUMS+E₂+ICI group（P<0.01）,the level of NE in the hippocampus decreased in OVX+CUMS+E₂+ICI group（P<0.05）.Conclusions:1.The decrease of estrogen level has a close relationship with the development of perimenopausal depression.2.OVX with CUMS may induce depression-like behaviors,and estrogen supplementation may alleviate depression-like behaviors in mice.3.The antidepressant effect of estrogen may be related to the up-regulation of5-HT and BDNF expression.4.The antidepressant effect of estrogen depends on the activation of estrogen receptors.