The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior.
The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior.
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DOI：
10.1038/tp.2015.35
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发表时间：
2015-04-07
影响因子：
6.8
通讯作者：
Muglia LJ
中科院分区：
文献类型：
--
作者：
Arnett MG;Pan MS;Doak W;Cyr PE;Muglia LM;Muglia LJ
早期生活压力（ELS）导致基因表达和行为的持续变化，增加了成年后患精神疾病的可能性。晚年精神病理学的神经生物学基础相对未知。目前的研究使用ELS小鼠模型，在出生后的前2周内每天进行母体分离，以测试杏仁糖皮质激素受体（GR）功能在介导冒险行为持续增加中的作用。ELS导致大脑中GR mRNA的减少，杏仁核的显著减少与焦虑，恐惧和社交样行为的持续改变有关。慢病毒介导的GR mRNA缺陷的恢复，特别是在成人杏仁核中央核（CeA）内，逆转了ELS后焦虑和社交行为的持久变化。这些结果提供了证据，持久的变化CeA GR神经回路ELS后，并建议GR调节过程中的CeA在调解ELS的终身适应不良行为的机制作用。我们证明，ELS的长期行为影响是可逆的，在以后的生活中，并牵连参与的CeA GR依赖活动的情绪持续失调ELS。
Early-life stress (ELS) leads to sustained changes in gene expression and behavior, increasing the likelihood of developing a psychiatric disorder in adulthood. The neurobiological basis for the later-in-life psychopathology is relatively unknown. The current study used a mouse model of ELS, achieved by daily maternal separations during the first 2 weeks of postnatal life, to test the role of amygdalar glucocorticoid receptor (GR) function in mediating the persistent increase in risk-taking behaviors. ELS produced a decrease in GR mRNA in the brain, with a notable reduction in the amygdala that was associated with sustained alterations in anxiety, fear and sociability-like behaviors. Lentiviral-mediated restoration of the GR mRNA deficit, specifically within the adult central nucleus of the amygdala (CeA), reversed the enduring changes in anxiety and social behavior after ELS. These results provide evidence of lasting changes in CeA GR neural circuitry following ELS and suggest a mechanistic role for GR-regulated processes in the CeA in mediating the lifelong maladaptive behaviors of ELS. We demonstrate that the long-lasting behavioral effects of ELS are reversible later in life and implicate the involvement of CeA GR-dependent activity in the sustained dysregulation of emotion following ELS.
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影响因子：
6.9
作者：
Kendler, KS;Sheth, K;Prescott, CA
通讯作者：
Prescott, CA
影响因子：
5.3
作者：
CAMPEAU, S;DAVIS, M
通讯作者：
DAVIS, M
DOI：
10.1111/j.1469-7610.1989.tb00770.x
发表时间：
1989-01-01
影响因子：
7.6
作者：
HODGES, J;TIZARD, B
通讯作者：
TIZARD, B
影响因子：
7.6
作者：
Caldji, C;Francis, D;Meaney, MJ
通讯作者：
Meaney, MJ
DOI：
10.1073/pnas.0803216105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Kolber, Benedict J.;Roberts, Marie S.;Muglia, Louis J.
通讯作者：
Muglia, Louis J.