Chunk #98 — 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) — Amygdala
This finding is consistent with prior work showing that ERK1/2 phosphorylation is reduced in the AMY following alcohol withdrawal and associated with increased anxiety-like behavior in rats (Pandey et al., 2008). In the present study, 3xTg-AD showed a similar pattern of results with reduced pERK1/2 expression in the AMY associated with enhanced cued fear response. Thus, dysregulation of ERK1/2 activity in the AMY may mediate heightened anxiety and fear related to AD pathology. Other evidence, however, shows that pERK1/2 is increased in the AMY of APPInd transgenic mice immediately after cued fear conditioning, suggesting that ERK signaling regulates enhanced fear response associated with AD (Espana et al., 2010). Interestingly, the observed decrease in pERK1/2 observed in the AMY of alcohol-exposed 3xTg-AD mice is similar to the effects of chronic unpredictable stress (Chandran et al., 2013). Thus, it will be important for future studies to evaluate pERK1/2 following cued fear conditioning in alcohol-exposed 3xTg-AD mice to determine if the observed basal downregulation is associated with insensitivity, or compensatory increased sensitivity, of ERK signaling under stressful conditions.
