Zinc Ameliorates LPS-Induced Depressive-Like Behaviors Via Modulating Microglial Polarization.

Abstract

The neuroinflammation plays a crucial role in the pathogenesis and progression of depression. Microglia serve as the principal source of neuroinflammatory factors and regulate neuroinflammation via M1 and M2 polarization phenotypes. Moreover, NOD like receptor protein 3 (NLRP3) inflammasome pathway is considered to be important in regulating pro-inflammatory cytokine release in the hippocampus. Zinc supplementation has been shown to effectively alleviate depressive symptoms in patients. In this study, we utilized a lipopolysaccharide (LPS)-induced mouse model of depression and LPS-activated BV-2 cells to examine the impact of zinc supplementation. The findings indicated that zinc supplementation could: (1) ameliorate the depressive-like behaviors of the mouse model with inhibition of inflammatory cytokines and zinc homeostasis recovery. (2) induce the polarization of microglia towards the M2 phenotype in vivo and in vitro. (3) suppress the activation of the NLRP3 inflammasome pathway by impeding the expression of P2X purinergic receptor 7 (P2 × 7) induced by LPS, thereby regulating microglial polarization. This may represent a crucial pathway via which zinc inhibits the M1 polarization of microglia, promotes polarization towards the M2 phenotype, thus improving neuroinflammation and exerting an antidepressant effect.