Effect of Alcohol on Brain Development

Abstract

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 con - sumption 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 neu - roimmune 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. synaptic plasticity and synaptic formation. Downregulation of genes by ethanol includes protein synthesis, myelination and the ubiquitin-proteasome pathway. Chronic ethanol exposure increases HMGB1–TLR4 and NF-κB signaling which leads to improved NF-κB target genes’ expression. This results in determining neuroimmune responses to ethanol toxicity that releases HMGB1 or directly stimulates TLR and/or NMDA receptors. An epigenetic mecha nism will show potential towards drug dependence by changing the DNA protein structure. Microglial cells will arbitrate the effect of alcohol toxicity on neurogenesis. The progression towards the neurobiologic techniques including micro array, QTL and proteomics will pro vide some anticipation for researching the molecular and cellular mechanisms that act as a keystone for the understanding of neuronal toxicity and enlightening new therapeutic gene targets for this public health burden.