Neuroimmune activation and myelin changes in adolescent rats exposed to high-dose alcohol and associated cognitive dysfunction: A review with reference to human adolescent drinking

Abstract

Aims: The aim of the study was to assess whether intermittent ethanol administration to adolescent rats activates innate immune response and TLRs signalling causing myelin disruption and long-term cognitive and behavioural deficits. Methods: We used a rat model of intermittent binge-like ethanol exposure during adolescence. Results: Binge-like ethanol administration to adolescent rats increased the gene expression of TLR4 and TLR2 in the prefrontal cortex (PFC), as well as inflammatory cytokines TNFα and IL-1β. Up-regulation of TLRs and inflammatory mediators were linked with alterations in the levels of several myelin proteins in the PFC of adolescent rats. These events were associated with previously reported long-term cognitive dysfunctions. Conversely, the same ethanol treatment did not cause significant changes in either inflammatory mediators or myelin changes in the brain of adult rats. Conclusion: Activation of innate immune receptors TLRs in the PFC appears to be involved in the neuroinflammation and demyelination processes induced by ethanol exposure during adolescence. The findings support the vulnerability of the juvenile brain to the effects of ethanol and the long-term cognitive consequences of binge drinking. In addition, ethanol-induced PFC dysfunctions might underlie the propensity of adolescents for impulsivity and to ignore the negative consequences of their behaviour, both of which could increase the risk of substance abuse. © The Author 2013. Medical Council on Alcohol and Oxford University Press. All rights reserved.