Ethanol-induced microglial activation is thought to be mediated by multiple immune receptor families, including TLRs (Alfonso-Loeches et al., 2010; Fernandez-Lizarbe et al., 2009). TLR4 KO prevents ethanol-induced changes in IBA1 immunoreactivity and protects against neurotoxicity in mouse cortex (Alfonso-Loeches et al., 2010). In microglial cells, ethanol up-regulates TLR4 and TLR2 and promotes a physical interaction between the two receptors that coincides with inflammatory mediator release (Fernandez-Lizarbe et al., 2013). NF-κB signaling, NADPH oxidase induction, and ROS production are all associated with changes in microglial morphology and neurodegeneration in ethanol-treated mice (Qin and Crews, 2012b).
