Abstract
Major depression disorder is a severe mental illness often linked with metabolic disorders. Adiponectin is an adipocyte-secreted circulatory hormone with antidiabetic and glucose/lipid modulation capacities. Studies have demonstrated the pathophysiological roles of adiponectin involved in various neurological disorders, including depression. However, the underlying mechanisms are poorly understood. Here we showed that adiponectin deprivation enhanced antidepressive-like behaviors in the LPS-induced model of depression. APN KO mice displayed increased cytokines (both pro and anti-inflammatory), accompanied by an impaired expression of adiponectin receptors (mRNA/protein level) and decreasing IBA-1 level in the cortex and primary microglia of LPS treated APN KO mice. Further, LPS-treatment significantly reduced p-NFκB expression in the microglia of APN KO mice. However, the Bay11-7082 treatment recovered p-NFκB expression in the cortex of APN KO mice in the presence of LPS. Interestingly, the antidepressant potentials of APN KO mice were abolished by TrkB antagonist K252a, IKK inhibitor Bay11-7082, and AdipoRon suggesting crosstalk between TrkB/BDNF signaling and NFκB in depression. Furthermore, the effects of Bay11-7082 were abolished by a TrkB/BDNF activator (7,8-DHF), indicating a critical role of TrkB/BDNF signaling. Taken together, these findings showed that dysregulated neuroinflammatory status and BDNF signaling might underlie the antidepressive-like behaviors of APN KO mice. NFκB elicited BDNF changes may be accountable for the pathogenesis of LPS induced depression, where APN might present an alternative therapeutic target for depressive disorders.