NIH-NIAAA recently funded a Chicago Alcohol Research Center entitled the “Center for Alcohol Research in Epigenetics” (CARE) to evaluate the epigenetic changes that are operative in the regulation of neurocircuitry function during the pathogenesis of alcoholism. The primary focus of CARE, under the direction of Dr. Subhash Pandey, is to investigate how different epigenetic mechanisms contribute to changes in specific target genes at the genome-wide level associated with adaptations in the reward and stress systems in the brain during alcoholism using clinical and preclinical models.
Alcohol abuse and alcoholism can be characterized by a pattern of compulsive alcohol consumption or loss of control over alcohol consumption by an individual. The euphoric or rewarding properties of alcohol on an individual occur through mesolimbic dopaminergic neurons projection from the ventral tegmental area (VTA) onto limbic brain regions. Several brain regions play a crucial role in regulating the negative affective (anxiety and depression) and positive affective states of alcohol addiction. Chronic alcohol use causes structural and functional changes in the frontal cortex, hippocampus and other cortico-limbic brain regions. Protein families such as histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and DNA demethylases are key players in chromatin remodeling in the genome.
CARE as a whole will identify the novel molecular targets within the epigenome, such as changes in HDACs and DNMTs, as well as DNA and histone methylation and demethylation networks, in several neurocircuitries affected during alcoholism to better understand the pathophysiology of alcoholism. CARE consists of four highly inter-related research projects and several pilot projects.