Alcohol's Toll on the Brain

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Science  28 Oct 2011:
Vol. 334, Issue 6055, pp. 435
DOI: 10.1126/science.334.6055.435-a

Toll-like receptor 4 (TLR4) is expressed by immune cells and controls the expression of genes related to the inflammatory response to pathogens. Wu et al. report that TLR4 and MyD88 (an adaptor protein that acts downstream of TLR4) are also involved in alcohol-induced behavioral changes in mice, implicating an inflammatory response in the brain to alcohol exposure. The duration of acute alcohol-induced sedation and impaired motor activity was reduced in mice lacking TLR4 or MyD88, and these mice recovered motor control more quickly than wild-type animals. Pharmacological inhibition of TLR4 before alcohol exposure also resulted in attenuated behavioral responses to alcohol. Analysis of hippocampal cells isolated from mice showed that alcohol increased the expression of IkBα (an inhibitor of the proinflammatory transcription factor NF-kB), an effect that depended on the presence of TLR4 or MyD88. Thus, a specific immune signaling pathway may be involved in a neuroinflammatory mechanism that controls behavioral responses to alcohol. These observations add to previous reports that in response to alcohol, TLR4 controls glial cell activity and cognitive functions in mice.

Br. J. Pharmacol. 10.1111/j.1476-5381.2011.01572.x (2011).

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