Environmental stressors and alcoholism development: Focus on molecular targets and their epigenetic regulation

Abstract

Alcohol exposure and stressful events in life can induce long-lasting changes in physiology, behavior and gene expression patterns, eventually facilitating the development of psychiatric diseases like alcohol use disorders (AUD). Epigenetic mechanisms have been recently proposed to play a role in the cellular actions of alcohol via chromatin remodeling. Here we discuss interactions between stress and the pharmacological effects of alcohol, including the possibility that early exposure to, or withdrawal of, alcohol might induce stressful effects of their own. A specific aim is to describe novel molecular mechanisms by which stress, alcohol or their combined presentation impact on the epigenome. A key question is why only a fraction of the population progresses from regular, non-problematic, alcohol use to AUD, despite suffering from similar alcohol exposure. It is important to analyze how environmental factors, most notably stress, interact with the epigenetic machinery to increase vulnerability for AUD. The knowledge derived from this endeavor will be critical for the development of preventive strategies and new, drug- or gene-based, therapies.

Epigenetic regulation of the cannabinoid receptor CB1 in an activity‐based rat model of anorexia nervosa

“…also play relevant roles in AN onset (Pjetri, Schmidt, Kas, & Campbell, 2012), even though the interaction with genetic factors is still to a large extent unexplored (Bouchard‐Mercier, Rudkowska, Lemieux, Couture, & Vohl, 2013; de Nadal, Ammerer, & Posas, 2011; Guarnieri et al, 2012; Mazzeo & Bulik, 2009). Environmental factors may influence gene function through epigenetic mechanisms (Bouchard‐Mercier et al, 2013; de Nadal et al, 2011; Guarnieri et al, 2012; Pucci, Micioni Di Bonaventura, Wille‐Bille, et al, 2019), and evoke transient changes in gene expression by causing chemical modifications of DNA without affecting DNA sequence of the organism. Several neurobiological systems related to mental disorders, energy homeostasis, hunger and feeding regulation have been hypothesized and/or reported to be involved in the development of AN (Rask‐Andersen, Olszewski, Levine, & Schioth, 2010).…”

Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

“…From the oxidation of 5mC by the Ten-Eleven Translocation (TET) enzymes, the 5-HydroxyMethylcytosine (5hmC) is formed. Given the associations of 5hmC with gene expression increase, it is now considered a novel epigenetic modification (Pucci et al, 2019).…”

Sobriety and Satiety: Is NAD+ the Answer?

“…Some epidemiological studies have suggested that addiction may be endemic in some populations [1]. The most common forms of addiction are alcoholism and smoking, both of which have been associated with increased risk of developing age-related disorders which manifest in the cardiovascular and central nervous system [2][3][4][5]. Tobacco smoking is the most preventable cause of morbidity and mortality worldwide.…”

“…Alcoholism is the third leading cause of death after cardiovascular disease and cancer and is associated with over 2.3 million deaths worldwide every year. Alcoholism is the ninth major contributor to global disease burden as measured by the disability-adjusted life years (DALYs) [2][3][4][5]. As with other forms of addiction, relapse occurs in response to exposure to environmental stimuli that are linked to the rewarding effects of the stimulant.…”