期刊
HUMAN MOLECULAR GENETICS
卷 25, 期 7, 页码 1370-1381出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddw019
关键词
-
资金
- National Institutes of Health [MH-084018, MH-094268, MH-069853, MH-085226, MH-088753, MH-092443, DA-040127, K99MH-094408]
- Brain & Behavior Research Foundation
- Stanley Foundation
- RUSK Foundation
- S-R Foundation
- Maryland StemCell Research Fund
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency Precursory Research for Embryonic Science and Technology
The molecular basis of vulnerability to stress during the adolescent period is largely unknown. To identify potential molecular mediators that may play a role in stress-induced behavioral deficits, we imposed social isolation on a genetically vulnerable mouse model. We report that 3-week (5-8weeks of age) adolescent stress in combination with disrupted-in-schizophrenia 1 (Disc1) genetic risk elicits alterations in DNA methylation of a specific set of genes, tyrosine hydroxylase, brain-derived neurotrophic factor and FK506 binding protein 5. The epigenetic changes in the mesocortical dopaminergic neurons were prevented when animals were treated with a glucocorticoid receptor (GR) antagonist RU486 during social isolation, which implicates the role for glucocorticoid signaling in this pathological event. We define the critical period of GR intervention as the first 1-week period during the stress regimen, suggesting that this particular week in adolescence may be a specific period of maturation and function of mesocortical dopaminergic neurons and their sensitivity to glucocorticoids. Our study may also imply the clinical significance of early detection and prophylactic intervention against conditions associated with adolescent social stress in individuals with genetic risk.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据