Differential effects of moderate chronic ethanol consumption on neurobehavior, white matter glial protein expression, and mTOR pathway signaling with adolescent brain maturation.

Adolescent brains are highly vulnerable to heavy alcohol exposure. Increased understanding of how alcohol adversely impacts brain maturation may improve treatment outcomes. This study characterizes short-term versus long-term effects of ethanol feeding on behavior, frontal lobe glial proteins, and mTOR signaling. Adolescent rats (8/group) were fed liquid diets containing 26% or 0% ethanol for 2 or 9 weeks, then subjected to novel object recognition (NOR) and open field (OF) tests. Frontal lobes were used for molecular assays. Significant ethanol effects on OF performance occurred in the 2-week model ( < .0001). Further shifts in OF and NOR performance were unrelated to ethanol exposure in the 9-week models ( < .05 to  < .0001). Ethanol inhibited MAG1 ( < .01) and MBP ( < .0001) after 2 but not 9 weeks. However, both control and ethanol 9-week models had significantly reduced MAG1 ( < .001-0.0001), MBP ( < .0001), PDGFRA ( < .05-0.01), and PLP ( < .001-0.0001) relative to the 2-week models. GFAP was the only glial protein significantly inhibited by ethanol in both 2- ( < .01) and 9-week ( < .05) models. Concerning the mTOR pathway, ethanol reduced IRS-1 ( < .05) and globally inhibited mTOR ( < .01 or  < .001) in the 9- but not the 2-week model. Short-term versus long-term ethanol exposures differentially alter neurobehavioral function, glial protein expression, and signaling through IRS-1 and mTOR, which have known roles in myelination during adolescence. These findings suggest that strategies to prevent chronic alcohol-related brain pathology should consider the increased maturation-related vulnerability of adolescent brains.