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

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Neuroinflammation, driven by microglia, is key in depression pathogenesis.
• The NLRP3 inflammasome pathway and microglial M1/M2 polarization are critical regulators of neuroinflammation.
• Zinc supplementation shows promise in alleviating depressive symptoms.

Purpose of the Study:

• To investigate the effects of zinc supplementation on a lipopolysaccharide (LPS)-induced mouse model of depression and BV-2 cells.
• To elucidate the mechanisms underlying zinc's antidepressant effects, focusing on neuroinflammation and microglial polarization.

Main Methods:

• Utilized an LPS-induced mouse model of depression and LPS-activated BV-2 microglial cells.
• Assessed depressive-like behaviors, inflammatory cytokine levels, zinc homeostasis, microglial polarization (M1/M2), and NLRP3 inflammasome activation.
• Examined the role of P2X7 receptor in LPS-induced NLRP3 inflammasome activation.

Main Results:

• Zinc supplementation ameliorated depressive-like behaviors, reduced inflammatory cytokines, and restored zinc homeostasis in the mouse model.
• Zinc induced microglial polarization towards the M2 phenotype both in vivo and in vitro.
• Zinc suppressed LPS-induced NLRP3 inflammasome activation by impeding P2X7 receptor expression, thereby regulating microglial polarization.

Conclusions:

• Zinc supplementation exerts antidepressant effects by mitigating neuroinflammation.
• Zinc promotes M2 microglial polarization and inhibits M1 polarization via suppression of the NLRP3 inflammasome pathway.
• Targeting zinc homeostasis and microglial polarization presents a potential therapeutic strategy for depression.