Chunk #99 — Results and discussion — Analysis of Akt/mTOR phosphoprotein pathway throughout the brain after chronic alcohol: Decreased expression of multiple mTOR/Akt phosphoproteins in 3xTg-AD alcohol-exposed mice (1-month post alcohol) — Conclusions
The mTOR/Akt pathway is critical in the regulation of cell growth, proliferation, and macroautophagy. The pathway is inextricably linked to aging and is regulated by growth factors, glucose, insulin, and stress. Aberrant signaling of the mTOR/Akt pathway has been implicated in human studies of AD and in numerous animal models, though the literature isn’t consistent about specific increases or decreases of total or phosphorylated proteins. To account for this discrepancy, it has been proposed that Akt/mTOR phosphorylation is decreased in neurons that are sensitive to AD and increased or maintained in neurons that are insensitive to AD (Pei & Hugon, 2008). Consistent with this premise, the present study found evidence for no change, significant decreases, and trends for increased phosphorylation in the Akt/mTOR pathway that was protein- and brain region-dependent. Moreover, the present study evaluated phosphorylation of Akt/mTOR signaling proteins in relatively young 3xTg-AD mice (8 months of age) at 1-month after alcohol exposure, which may reflect direct long-lasting effects of alcohol or compensatory changes. For these reasons, we suggest that understanding the impact of alcohol drinking on the Akt/mTOR
