Differential effects of moderate chronic ethanol consumption on neurobehavior, white matter glial protein expression, and mTOR pathway signaling with adolescent brain maturation.
Am J Drug Alcohol Abuse
; 50(4): 492-516, 2024 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-38847790
ABSTRACT
Background:
Adolescent brains are highly vulnerable to heavy alcohol exposure. Increased understanding of how alcohol adversely impacts brain maturation may improve treatment outcomes.Objectives:
This study characterizes short-term versus long-term effects of ethanol feeding on behavior, frontal lobe glial proteins, and mTOR signaling.Methods:
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.Results:
Significant ethanol effects on OF performance occurred in the 2-week model (p < .0001). Further shifts in OF and NOR performance were unrelated to ethanol exposure in the 9-week models (p < .05 to p < .0001). Ethanol inhibited MAG1 (p < .01) and MBP (p < .0001) after 2 but not 9 weeks. However, both control and ethanol 9-week models had significantly reduced MAG1 (p < .001-0.0001), MBP (p < .0001), PDGFRA (p < .05-0.01), and PLP (p < .001-0.0001) relative to the 2-week models. GFAP was the only glial protein significantly inhibited by ethanol in both 2- (p < .01) and 9-week (p < .05) models. Concerning the mTOR pathway, ethanol reduced IRS-1 (p < .05) and globally inhibited mTOR (p < .01 or p < .001) in the 9- but not the 2-week model.Conclusions:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Neuroglia
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Etanol
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Serina-Treonina Quinases TOR
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Substância Branca
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article