Estrogen Plays An Antidepressant Role By Regulating ERK-BDNF Signaling Pathway Of LHb

Depression has attracted widespread attention due to its heavy incidence,which brings heavy psychological and economic burden to families and individuals.It has been reported that 17β-estrogen（E₂）plays an antidepressant effect,but the molecular mechanism of its antidepressant effect remains to be elucidated.which is located in thalamus,the Lateral Habenula（LHb）is closely related to depression.LHb contains Estrogen Receptor（ER）,and Estrogen can affect LHb neuronal activity.However,it is not clear whether Estrogen plays an anti-depression role on LHb,so Western Blot and behavior tests are applied in this study.The results showed that:ovariectomized mice showed significant depression-like behavior,including longer time in forced swimming test and reduced total movement distance in the open field test,while intraperitoneal injection of estrogen could improve the depression-like behavior of mice;in ovariectomy group,the expression of p-ERK and BDNF（Brain Derived Neurotrophic Factors）and c-Fos of LHb was significantly increased compared with ovariectomy+estrogen group and sham operation control group.Microinjection of estrogen into LHb of ovariectomy mice significantly improved depression-like behavior and decreased ACTH（Adrenocorticotropic Hormone）in blood.LHb can be used as a target of estrogen to mediate the antidepressant effect of estrogen,and its mechanism may be realized by affecting the ERK-BDNF signaling pathway,or it may be related to reducing the function of HPA axis.This study provides a new explanation for the pathogenesis of depression caused by decreased estrogen level,and provides a new target for clinical prevention and treatment.