Histone Modifications in Major Depressive Disorder and Related Rodent Models

Advances in Experimental Medicine and Biology
Jan M Deussing, Mira Jakovcevski

Abstract

Major depressive disorder (MDD) is a multifactorial disease, weakly linked to multiple genetic risk factors. In contrast to that, environmental factors and "gene × environment" interaction between specific risk genes and environmental factors, such as severe or early stress exposure, have been strongly linked to MDD vulnerability. Stressors can act on the interface between an organism and the environment, the epigenome. The molecular foundation for the impact of stressors on the risk to develop MDD is based on the hormonal stress response itself: the glucocorticoid receptor (GR, encoded by NR3C1). NR3C1 can directly interact with the epigenome in the cell nucleus. Besides DNA methylation, histone modifications have been reported to be crucial targets for the interaction with the stress response system. Here, we review critical findings on the impact of the most relevant histone modifications, i.e. histone acetylation and methylation, in the context of MDD and related animal models. We discuss new treatment options which have been based on these findings, including histone deacetylase inhibitors (HDACis) and drugs targeting specific histone marks, closely linked to psychiatric disease. In this context we talk about contemporary ...Continue Reading

Citations

Aug 16, 2018·Physiological Reviews·Jan M Deussing, Alon Chen
Mar 6, 2019·Frontiers in Behavioral Neuroscience·Jessica L BoltonTallie Z Baram
Jun 6, 2020·Frontiers in Psychiatry·Maria Salud García-GutiérrezJorge Manzanares
May 7, 2020·Depression Research and Treatment·Monika Talarowska
Dec 19, 2018·Cell and Tissue Research·Jaanus Harro
Jun 30, 2018·Molecular Psychiatry·Gabor EgervariYasmin L Hurd
Jun 3, 2021·International Journal of Molecular Sciences·Hyun-Sun ParkHong-Yeoul Ryu
Dec 6, 2018·Neuroimmunomodulation·Ana Clara LibermanClaudio A Serfaty
Nov 23, 2021·Frontiers in Neuroscience·Julia Reichard, Geraldine Zimmer-Bensch

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