Chunk #88 — 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)
To gain further understanding of the long-lasting impact of chronic nondependent alcohol drinking on molecular mechanisms of AD, we assessed the phosphorylation state of the Akt/mTOR cell signaling pathway. Akt/mTOR signaling regulates a wide array of molecular and cellular functions in the brain including nutrient uptake, glucose metabolism, cell growth and survival, transcription and migration (Yu & Cui, 2016). Importantly, the Akt/mTOR pathway is implicated in AD pathology in humans and animal models (Oddo, 2012) and alcohol addiction (Neasta, Barak, Hamida, & Ron, 2014). For example, glycogen synthase kinase-3 (GSK3) is critical to the hyperphosphorylation of Tau, has been linked to increased Aβ production, and Aβ mediated cell death (Avila et al., 2012; de la Monte et al., 1999; Hernandez, 2013; Hooper, Killick, & Lovestone, 2008). GSK3 also regulates the positive reinforcing effects of alcohol and is sensitive to acute alcohol treatment and withdrawal (Faccidomo et al., 2019; Neasta, Ben Hamida, Yowell, Carnicella, & Ron, 2011; van der Vaart et al., 2018). Additional proteins in the mTOR/Akt pathway such as Akt, PTEN, p70S6K, RPS6, ERK1/2 and mTOR are targets of
