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.
OBJECTIVE
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.


CONCLUSIONS
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.
Corresponding author: Department of Cellular Pathology, Centro de Investigación Príncipe Felipe, C/ Eduardo Primo Yúfera 3, 46012 Valencia, Spain. guerri@cipf.es.
María
M
Pascual
Antoni
A
Pla
José
J
Miñarro
Consuelo
C
Guerri
D000293:Adolescent; D000428:Alcohol Drinking / Q000276:immunology*; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology* / Q000276:immunology*; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D018836:Inflammation Mediators / Q000276:immunology; D009186:Myelin Sheath / Q000187:drug effects* / Q000276:immunology; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
D018836:Inflammation Mediators; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000431:Ethanol