miR-124 ameliorates depressive-like behavior by targeting STAT3 to regulate microglial activation

Area of Science:

• Neuroscience
• Molecular Biology
• Psychiatry

Background:

• Major depressive disorder (MDD) is a prevalent global health concern with complex, variable treatment responses.
• Dysfunctional microRNAs (miRNAs), including brain-enriched miR-124, are implicated in MDD pathogenesis.
• miR-124's specific role and therapeutic potential in depression require further elucidation.

Purpose of the Study:

• To investigate the role of miR-124 in a mouse model of depression.
• To explore the underlying molecular mechanisms of miR-124 in regulating depressive-like behaviors and neuroinflammation.

Main Methods:

• Utilized a chronic unpredictable mild stress (CUMS) mouse model to induce depressive-like behaviors.
• Assessed miR-124 levels in the hippocampus and its effect on microglial activation.
• Investigated miR-124's direct targeting of STAT3 in BV2 microglial cells and its impact on inflammatory cytokine production.

Main Results:

• miR-124 expression was downregulated in the hippocampus of CUMS-exposed mice.
• Restoring miR-124 expression ameliorated depressive-like behaviors and reduced CUMS-induced microglial activation.
• miR-124 directly targets STAT3, and its upregulation inhibited pro-inflammatory mediators in LPS-stimulated BV2 cells.

Conclusions:

• miR-124 dysfunction contributes to depression development by promoting microglial activation.
• miR-124 serves as a potential therapeutic target and biomarker for major depressive disorder.
• Targeting miR-124 may offer a novel strategy for treating depression by modulating neuroinflammation.