rs-504393 and Encephalitis

Neuroinflammation and microglial activation have been implicated in both alcohol use disorders (AUD) and fetal alcohol spectrum disorders (FASD). Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. FASD is the leading cause of mental retardation, and one of the most devastating outcomes of FASD is the loss of neurons in the central nervous system (CNS). The underlying molecular mechanisms, however, remain unclear. We hypothesize that MCP-1/CCR2 signaling mediates ethanol-induced neuroinflammation and microglial activation, which exacerbates neurodegeneration in the developing brain.. MCP-1/CCR2 signaling played an important role in ethanol-induced microglial activation/neuroinflammation and neurodegeneration in the developing brain. The effects may be mediated by the interaction among MCP-1/CCR2 signaling, TLR4, and GSK3β.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Benzoxazines; Brain; Caspase 3; Cells, Cultured; Central Nervous System Depressants; Chemokine CCL2; Disease Models, Animal; Encephalitis; Ethanol; Gene Expression Regulation, Developmental; Indazoles; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Neurodegenerative Diseases; Propionates; Receptors, CCR2; Signal Transduction; Spiro Compounds