Chunk #92 — 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) — Hippocampus
These results indicate that a history of alcohol drinking is associated with downregulation of Akt/mTOR phospho-signaling in subregions of the HPC in 3xTg-AD mice. The impact of alcohol was selective to the LHPC (IRS1 and p70S6K) and CA1 (mTOR and PTEN). This is consistent with evidence showing that levels of p-mTOR (Ser2448) and p70S6K (Thr389) are decreased in the cortex of double APP/PS1 transgenic mice as compared to WT controls (Lafay-Chebassier et al., 2005). Similarly, treatment of SH-SY5Y with 20μM Aβ decreases p-mTOR (Ser2448) expression, and pharmacological inhibition of mTOR induced cell death (Lafay-Chebassier et al., 2006). However, other reports show increased mTOR or PTEN in AD and mixed results in the alcohol literature (Caccamo, Belfiore, & Oddo, 2018; Fu et al., 2016; Griffin et al., 2005; Hagner et al., 2009; Li & Ren, 2007; Norambuena et al., 2017; Oddo, 2012; Tramutola et al., 2015; Wang et al., 2014). Thus, it will be critical for future studies to carefully parse out changes in these phosphoproteins due to AD pathology, long-term alcohol, and normal aging.
