Attenuation of microglial and IL-1 signaling protects mice from acute alcohol-induced sedation and/or motor impairment

Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction?

“…Studies of microglial contributions to psychiatric disorders have only recently begun (Monji et al 2009). Recent PET imaging studies report that microglial activation has appeared in the brains of acute phase patients with schizophrenia (Doorduin et al 2009;Takano et al 2010;van Berckel et al 2008), methamphetamine users , alcoholics (He and Crews 2008;Wu et al 2011), and suicide patients (Steiner et al 2006(Steiner et al , 2008. Emotional dysregulation is often a factor in various psychiatric illnesses, including suicide (Mann et al 2005).…”

Molecular basis of alcoholism

“…Acute and chronic alcohol use activates microglia, the resident macrophages of the brain, and increases proinflammatory cytokines via nuclear factor κ B (NFκB) in the brain (Crews et al, 2011). Behavioral responses to acute alcohol were altered in mice that are lacking TLR receptors, TLR2 or TLR4 (Wu et al, 2011). In a key publication, the knockdown of TLR4 in the rat amygdala using siRNA decreased alcohol self-administration, demonstrating that neuroimmune signaling independent of input from peripheral cytokines was sufficient in regulating alcohol behavior (Liu et al, 2011).…”

Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond

“…67 Recently, we have shown that ethanol also interacts with the TLR4-regulated inflammatory cascade. 68 Collectively, this raises the reasonable prospect that environmental factors such as excessive alcohol intake, stress or chemical toxins can cause a state of chronic 'sterile inflammation' by eliciting release of local or circulating intrinsic factors that bind TLRs on uterine cells, in turn impacting cytokine synthesis to adversely influence embryo development and ⁄ or endometrial receptivity in a manner similar to pathogen-associated TLR ligands. While DAMPs activate TLRs using overlapping but also distinct co-receptors, molecular pathways and intracellular machinery to PAMPs, ligation culminates in activation of the NFjB and IRF transcription factors and release of similar proinflammatory cytokines including TNFA and IFNG.…”