Towards unraveling ethanol-specific neuro-metabolomics based on ethanol responsive genes in vivo.

The search for genetic causes involved in alcohol dependence/response has been challenging. Understanding the mechanisms of action and interaction of the genes implicated in alcohol response is a key towards understanding the problem. Sixty-nine ethanol responsive genes were used in a detailed genome-wide examination to study their neuro-metabolomics. These genes displayed very close interactions among themselves with over 400 regulation events and 100 expression events contributing to 15 different cell processes including cell signaling, transport and proliferation. Acute ethanol produces a global effect on the neuro-metabolome. Ethanol alone was found to interact with over 1000 genes and cell events. The study revealed that the ethanol responsive genes directly regulate and are themselves regulated by the activity of other proteins and cell processes. We propose a pathway involving nine interacting ethanol responsive genes, which may determine differential ethanol effects in the brain in vivo.