Prior history of chronic stress changes the transcriptional response to glucocorticoid challenge in the dentate gyrus region of the male rat hippocampus

Publication Type:

Journal Article


Endocrinology (2013)


1945-7170 (Electronic)00

DOI Name (links to online publication)



Chronic stress is a risk factor for several neuropsychiatric diseases such as depression and psychosis. In response to stress glucocorticoids (GCs) are secreted that bind to the glucocorticoid receptor (GR), a ligand-activated transcription factor that regulates the transcription of gene networks in the brain necessary for coping with stress, recovery and adaptation. Chronic stress particularly affects the dentate gyrus (DG) subregion of the hippocampus, causing several functional and morphological changes with consequences for learning and memory, that are likely adaptive, but at the same time make DG neurons more vulnerable to subsequent challenges.The aim of this study was to investigate the transcriptional response of DG neurons to a GC-challenge in male rats previously exposed to chronic restraint stress (CRS). An intriguing finding of the current study was that having a history of CRS had profound consequences for the subsequent response to acute GC-challenge, differentially affecting the expression of several hundreds of genes in the DG compared to challenged non-stressed control animals. This enduring effect of prior stress exposure suggests that epigenetic processes may be involved. In line with this, CRS indeed affected the expression of several genes involved in chromatin structure and epigenetic processes, including Asf1, Ash1l, Hist1h3f and Tp63. The data presented here indicate that CRS alters the transcriptional response to a subsequent GC-injection. We propose that this altered transcriptional potential forms part of the molecular mechanism underlying the enhanced vulnerability for stress-related disorders like depression caused by chronic stress.