View : 928 Download: 0
Stress-Induced Epigenetic Changes in Hippocampal Mkp-1 Promote Persistent Depressive Behaviors
- Title
- Stress-Induced Epigenetic Changes in Hippocampal Mkp-1 Promote Persistent Depressive Behaviors
- Authors
- Lee, Jung-Eun; Kwon, Hye-Jin; Choi, Juli; Han, Pyung-Lim
- Ewha Authors
- 한평림
- SCOPUS Author ID
- 한평림
- Issue Date
- 2019
- Journal Title
- MOLECULAR NEUROBIOLOGY
- ISSN
- 0893-7648
1559-1182
- Citation
- MOLECULAR NEUROBIOLOGY vol. 56, no. 12, pp. 8537 - 8556
- Keywords
- Stress adaptation; Epigenetic factors; HDAC2; Mkp-1
- Publisher
- SPRINGER
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Chronic stress induces persistent depressive behaviors. Stress-induced transcriptional alteration over the homeostatic range in stress hormone-sensitive brain regions is believed to underlie long-lasting depressive behaviors. However, the detailed mechanisms by which chronic stress causes those adaptive changes are not clearly understood. In the present study, we investigated whether epigenetic changes regulate stress-induced depressive behaviors. We found that chronic stress in mice downregulates the epigenetic factors HDAC2 and SUV39H1 in the hippocampus. A series of follow-up analyses including ChIP assay and siRNA-mediated functional analyses reveal that glucocorticoids released by stress cumulatively increase Mkp-1 expression in the hippocampus, and increased Mkp-1 then debilitates p-CREB and PPAR gamma, which in turn suppress the epigenetic factors HDAC2 and SUV39H1. Furthermore, HDAC2 and SUV39H1 normally suppress the transcription of the Mkp-1, and therefore the reduced expression of HDAC2 and SUV39H1 increases Mkp-1 expression. Accordingly, repeated stress progressively strengthens a vicious cycle of the Mkp-1 signaling cascade that facilitates depressive behaviors. These results suggest that the hippocampal stress adaptation system comprising HDAC2/SUV39H1-regulated Mkp-1 signaling network determines the vulnerability to chronic stress and the maintenance of depressive behaviors.
- DOI
- 10.1007/s12035-019-01689-4
- Appears in Collections:
- 일반대학원 > 뇌·인지과학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML