دانلود رایگان مقاله انگلیسی پیشرفت در اپی ژنتیک افسردگی - الزویر 2018

Abstract

Depression is a prevalent and complex psychiatric syndrome. Epigenetic mechanisms bridge the genetic and environmental factors that contribute to the pathophysiology of depression. A surge of research over the last decade has identified changes in DNA methylation, histone modifications, histone organization, and noncoding RNAs associated with depression and stress-induced depression-like behavior in animal models. We focus here on associations of epigenetic factors concurrent with depression and depression-like behavior, although risk for depression and some of the associated epigenetic changes are known to have developmental origins. Finally, emerging technology may enable breakthroughs in the ability to rescue depression-associated epigenetic modifications at specific genes, greatly enhancing specificity of future potential therapeutic treatments.

9. CONCLUSIONS

Looking toward the future, it will be important for studies to integrate peripheral epigenetic modifications—DNA methylation and noncoding RNAs in particular—with changes within the brain, across relevant brain regions. An essential challenge in neuropsychiatry moving forward is to increase the cell-type specificity of studies of epigenetic modifications within the brain. Epigenetic changes are known to be specific to developmental stage, tissue or region, and cell type, and studies are just now beginning to measure and manipulate epigenetic mechanisms with this resolution. Furthermore, in order to push the field forward constant dialogue is needed between human and animal researchers. Model systems enable researchers to test the functional relevance of findings from human studies to determine whether identified epigenetic alterations are correlative or causative. Finally, there is an urgent demand for increased specificity in animal studies testing the causative nature of epigenetic changes. Manipulation of DNMTs or HATs, for example, will have genome-wide impact, yet sequencing studies are increasingly revealing specificity in epigenetic regulation. Recent developments in molecular tools, including zinc finger proteins, transcription activator-like effectors (TALES), and CRISPR now enable researchers to target individualgenes for a single type of epigenetic modification.