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Review
.2014 Apr 4:264:198-206.
doi: 10.1016/j.neuroscience.2013.07.064. Epub 2013 Aug 3.

Mechanisms of transgenerational inheritance of addictive-like behaviors

Affiliations
Review

Mechanisms of transgenerational inheritance of addictive-like behaviors

F M Vassoler et al. Neuroscience..

Abstract

Genetic factors are implicated in the heritability of drug abuse. However, even with advances in current technology no specific genes have been identified that are critical for the transmission of drug-induced phenotypes to subsequent generations. It is now evident that epigenetic factors contribute to disease heritability and represent a link between genes and the environment. Recently, epigenetic mechanisms have been shown to underlie drug-induced structural, synaptic, and behavioral plasticity by coordinating the expression of gene networks within the brain. Therefore, the epigenome provides a direct mechanism for drugs of abuse to influence the genetic events involved in the development of addiction as well as its heritability to subsequent generations. In this review we discuss the mechanisms underlying intergenerational epigenetic transmission, highlight studies that demonstrate this phenomenon with particular attention to the field of addiction, and identify gaps for future studies.

Keywords: BDNF; cocaine; epigenetics; prefrontal cortex; transgenerational inheritance.

Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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Figures

Figure 1
Figure 1. Schematic representation of the epigenetic mechanisms involved in transgenerational epigenetic inheritance
Environmental stimuli such as diet, toxins, stress, and drugs of abuse lead to epigenetic changes in the germline of the exposed individual that can be transmitted to the subsequent generations. Epigenetic alterations that have thus far been described include, changes in DNA methylation (yellow circles with methyl groups); repressive histone marks (H3K9me3, H3K27me3; red); permissive histone marks (H3K4me2/3, H3K9K14ac2, H3K36me3; green), and noncoding RNAs (miRNA, piRNA). Abbreviations: miRNA, microRNAs; piRNA, Piwi-interacting RNAs.
Figure 2
Figure 2. Schematic representation of epigenetic changes in F0 and F1 male rats following paternal cocaine self-administration
Cocaine self-administration in male rats increases BDNF protein and exon IV transcript levels in the medial prefrontal cortex (mPFC) of rats. These changes are associated with increased H3K9K14ac2 association with BDNF promoter IV. Moreover, there is an increase in total H3K9K14ac2 in the testes as well as associated with BDNF promoters in the sperm of F0 rats. The same molecular alterations are measured in the mPFC of F1 male offspring. In addition, H3K9K14ac2 levels are also increased in the testes of the F1 animals, suggesting that H3K9K14ac2 may be a critical epigenetic mechanism for the transmission of this phenotype. Abbreviations: BDNF, brain-derived neurotrophic factor; H3K9K14ac2, di-acetyl lysine 9, lysine 14, histone H3; mPFC, medial prefrontal cortex.
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