17β-Estradiol (E2) Alleviates Depressive-Like Behaviors By Inhibiting Gp130/JAK1/STAT3 Signaling Pathway Through Estrogen Receptor-β

Abstract Background: Neuroinflammation has an important role in the pathogenesis of depression, and estrogen can inhibit the secretion of inflammatory factors IL-6 and TNF-and relieve depression-like behaviors in MDD patients. The gp130 / JAK1 / STAT3-mediated neuroinflammation plays an important role in the pathogenesis of depression. Exploring the specific mechanism of estrogen inhibition of neuroinflammation in depression has a positive effect on the treatment of MDD.Methods: Wild-type female C57BL / 6 mice were randomly divided into control mice, OVX mice and OVX + E2 mice, and OVX + E2 mice were pretreated with a 0.2 mg/kg/day dose for one month to observe their depression-like behavior. In addition, E2 was also used to interfere with the BV2 cells. Intraperitoneal injection of E2 after OVX confirmed the therapeutic effect of E2 and further verified the molecular mechanism of E2.Results: the inflammatory response and impairment was significantly reduced and the depression-like behavior was alleviated in OVX+E2 group. Moreover, gp130 / JAK1 / STAT3 signaling pathway was also downregulated. On the other hand, hippocampal apoptosis was significantly reduced in mice in the OVX + E2 group. We further demonstrated that E2 inhibited gp130 / JAK1 / STAT3 signaling pathway via estrogen receptor-β (ER-β).Conclusion: we confirmed the anti-depressant effect and anti-apoptotic of E2 we verified that E2 alleviated inflammatory response and depressive-like behaviors by inhibiting gp130/JAK1/STAT3 signaling pathway via combining with ER-β and gp130. This study suggested that E2 exerted neuroprotective effects and estrogen replacement therapy will be a promising therapeutic strategy to alleviate neuroinflammation and depressive-like behaviors.