The Phagocytic Receptor MERTK Mediates Lycopene's Ameliorative Effects on Atrazine-Induced Microglial Efferocytosis...

Atrazine (ATZ), a widely used herbicide, induces neurotoxicity by disrupting microglial efferocytosis─a critical process for maintaining central nervous system homeostasis. Lycopene (LYC), a natural antioxidant, exhibits protective potential against pesticide-induced damage, yet its role in ATZ-impaired efferocytosis remains unexplored. Here, we demonstrate that LYC mitigates ATZ-induced hippocampal neuroinflammation and microglial dysfunction in mice. ATZ exposure triggered M1 polarization of microglia, apoptosis, and mitochondrial damage, accompanied by suppressed efferocytosis. However, LYC treatment significantly reduced pro-inflammatory cytokine levels (TNF-α, CD68), enhanced anti-inflammatory markers (IL-10, TGF-β), and restored mitochondrial integrity. Mechanistically, LYC upregulated MERTK expression (phagocytic receptor), facilitating microglial efferocytosis via enhanced IBA-1/MERTK colocalization. Molecular docking revealed a strong binding affinity between LYC and MERTK (-8.9 kcal/mol), suggesting direct interaction. These findings highlight MERTK as a novel target for LYC-mediated neuroprotection against ATZ toxicity, providing insights into potential dietary interventions for pesticide-associated neurological disorders.