A Brief Review on Epigenetic Aspects involved in Depression

Abstract

It is known that external environmental or internal physiologic factors interact with an individual's genetic constitution to determine risk for depression throughout life. This can be possible through epigenetic mechanisms that lead to changes in gene expression -with transgenerational abilities -that do not involve a change in the DNA sequence. Here we briefly summarize the link between depressive disorders and epigenetics, considering stressful events as important triggers for these modifications. The increasing knowledge in this issue is relevant for updating and expanding comprehension in the molecular basis of this mood disorder. Keywords Epigenetic aspects involved in depressionGrowing evidences support the hypothesis that epigenetics is a key mechanism through which environmental exposures interact with our genetic constitution and this interaction is able to cause depression throughout life. The term epigenetics ("epi" means above in Greek) is used to denote transgenerational transmission of traits without a change in the nucleotide sequence of DNA [1][2][3][4]. It had emerged as a mechanism initiated by environmental cues and cellular events mediated by various cellular mechanisms that originate phenotypes during the development. However, recently, it has been postulated that these cellular modifications can be converted into alterations in chromatin structure -non related with DNA sequence alteration -that finally lead to expression or suppression of altered gene programs [5].While the genome defines the potential genetic information, the epigenome defines which genes are actually expressed. This regulation over the gene expression without altering the sequence of the DNA is possible by epigenetic modifications including microRNAs (small RNA molecules that can negatively control their target gene expression posttranscriptionally), covalent modifications of histone proteins, mechanisms controlling higher order chromatin organization and DNA methylation. Among numerous epigenetic processes, DNA methylation is one of the major mechanisms studied in the context of early life adversities as a potential via to explain the long-term effects on gene transcription [3]. It is a stable mark that is important for diverse cellular processes [6]. Methyl group is added to the C5 position catalyzed by DNA methyltransferases (DNMTs) [7]. Considering all cytosines in the human genome, about 3% is methylated and proper cytosine methylation is required for cell differentiation, genetic imprinting and suppression of repetitive elements. In the central nervous system, DNA methylation is a physiological process, relevant for normal brain development, differentiation and maintenance of function [8,9]. Indeed, during development, pluripotent stem cells undergo division and differentiate into different cell types that ultimately become different organs and tissues with specific patterns of gene expression [10].Epigenetics refers to how both the external environment and internal physiologic environment can interact wit...