In the world, 3.3 million deaths occur every year due to harmful use of alcohol; this represents 5.9% of all deaths. Ethanol metabolites’ production and their post-translation modification are one of the proposed mechanisms that lead to neuronal toxicity. The projected neurochemical changes in chronic alcohol drinkers may be due to an imbalance between excitatory and inhibitory neurotransmitters. Interaction of alcohol with GABA and glutamate receptors (NMDA and AMPA) resulted in diverse adaptive changes in gene expression through neuronal pathways leading to alcohol toxicity. Alcohol consumption in an individual leads to biochemical changes that are correlated with complex inflammatory signaling pathways such as phosphorylation of proteins, synthesis of nitric oxide (NO), NF-kappaB and MAP kinase pathways in certain regions of the brain. Ethanol exposure activates neurons and microglial cells that lead to release of neuroimmune factors like high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4) and certain cytokines involved in immune responses leading to neuroimmune signaling in the brain. Epigenetic modification of DNA and histones may lead to neuronal gene expression, thus regulating ethanol toxicity. Researchers attempt to modulate therapies that can help to foil alcohol toxicity and support the development of original neuronal cells that have been injured or degenerated by alcohol exposure.
Part of the book: Drug Addiction