The Effect Of Estrogen And Dehydroepiandrosterone On Depression-like Behaviors In Ovariectomized Rats

Objective: Perimenopausal depressive disorder is a serious disease that can affect the physical and mental health of aged women.The sharp decrease and fluctuation of estrogen levels at this stage contribute to the disease.Dehydroepiandrosterone is a precursor of estrogen and can take its biological effect by converted into estrogen partially.In order to research the effect of estrogen and dehydroepiandrosterone on perimenopausal depression and metabolism,we took bilateral ovariectomy to establish perimenopause model in rats,and dehydroepiandrosterone was given intragastrically to observe lipid metabolism,glucose tolerance and depressive-like behaviors,further,to explore brain-derived neurotrophic factor(BDNF)signaling pathway and the the expression of estrogen receptors in hippocampus,which helped to investigate the effect of estrogen and dehydroepiandrosterone on metabolism and perimenopausal depressive disorder as well as the underlying mechanism.Methods: The animal models of perimenopausal depressive disorder was established by bilateral ovariectomy.Estrogen and dehydroepiandrosterone were given intragastrically for 12 weeks.Lipid metabolism disorder and glucose tolerance were measured,together with depressive-like behaviors.Further,BDNF levels and proteins in the signaling pathway together with estrogen receptor were measured in hippocampus.Following groups were designed in female SD rats: sham control group(Sham group),bilateral ovariectomized group(OVX group),bilateral ovariectomized + DHEA administration group(OVX + DHEA group),ovariectomized + estrogen administration group(OVX + E2 group).The concentration was 0.27 mg/kg for estrogen,and it was 13.3mg/kg for DHEA.The same bulk of saline were feed to Sham and OVX rats by gavage for 12 weeks.The body weight of the rats was recorded and the oral glucose tolerance were monitored after 12-week administration.Twelve weeks later,changes in depressive-like and anxiety-like behaviors in rats were monitored using the source preference test,open field test together with elevated plus-maze test and forced swimming test.Serum triglyceride,total cholesterol,high-density lipoprotein,and low-density lipoprotein were detected to explore the lipid metabolism after administration.Western blotting was used to detect the BDNF signaling pathway and estrogen receptor ? and ? expression in hippocampus of rats to explore the possible mechanism of estrogen and dehydroepiandrosterone.Results: 1.Estrogen and dehydroepiandrosterone supplement can reverse the weight change caused by ovariectomy.2.Estrogen supplement can partially improve the disorders of lipid metabolism and impaired glucose tolerance caused by ovariectomy,and dehydroepiandrosterone can reverse impaired glucose tolerance,but has no effect on lipid metabolism.3.Estrogen and dehydroepiandrosterone supplement can ameliorate depressive-like behavior in ovariectomized rats.4.Estrogen and dehydroepiandrosterone supplement can take effect through BDNF signaling pathway.5.Estrogen and dehydroepiandrosterone supplement increased the expression of estrogen receptor ? in the hippocampus,but there was no significant change in the expression of estrogen receptor ? in the hippocampus after ovariectomy.Conclusions: Summarizing above experimental results,bilateral ovariectomy can successfully establish a perimenopausal model in rats.Rats will experience weight gain,abnormal lipid metabolism,impaired glucose tolerance and depression-like behavior.And estrogen and dehydroepiandrosterone supplement can reverse these changes to some extent.Estrogen and dehydroepiandrosterone may play an antidepressant role by increasing brain-derived neuroprotective factor BDNF signaling pathway and regulating estrogen receptor beta.Thus,dehydroepiandrosterone may play a similar role as estrogen in the treatment of depression in perimenopause,providing a choice for the treatment of perimenopause depression.