| Autor: |
Yalcin EB; Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Lifespan Academic Institutions, The Providence VA Medical Center, The Warren Alpert Medical School of Brown University, Providence, RI, USA., Tong M; Department of Medicine, Rhode Island Hospital, Lifespan Academic Institutions, The Warren Alpert Medical School of Brown University, Providence, RI, USA., Delikkaya B; Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Lifespan Academic Institutions, The Providence VA Medical Center, The Warren Alpert Medical School of Brown University, Providence, RI, USA., Pelit W; Department of Chemistry, Brown University, Providence, RI, USA., Yang Y; Biotechnology Graduate Program, Brown University, Providence, RI, USA., de la Monte SM; Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Lifespan Academic Institutions, The Providence VA Medical Center, The Warren Alpert Medical School of Brown University, Providence, RI, USA.; Department of Medicine, Rhode Island Hospital, Lifespan Academic Institutions, The Warren Alpert Medical School of Brown University, Providence, RI, USA.; Departments of Neurology and Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA. |
| Abstrakt: |
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. |
