Trans-generational effects of early life stress: the role of maternal behavior.
Trans-generational effects of early life stress: the role of maternal behavior.
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DOI：
10.1038/srep04873
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发表时间：
2014-05-02
影响因子：
4.6
通讯作者：
Medina LR
中科院分区：
文献类型：
--
作者：
Schmauss C;Lee-McDermott Z;Medina LR
使用早期生活压力、婴儿母体分离 (IMS) 的啮齿动物范例，我们检查了 IMS 触发的应激敏感小鼠品系 Balb/c 的行为和表观遗传表型是否会代代相传。这些表型包括成年期情绪行为受损和执行认知功能缺陷，并且它们与前脑新皮质中组蛋白 H4K12 蛋白 (acH4K12) 的乙酰化增加有关。这些行为和表观遗传表型会传递给 IMS Balb/c 母亲的第一个后代，但不会传递给父亲，交叉寄养实验表明，这种传递是由母体行为触发的，并受到幼崽遗传背景的调节。在原始应激源持续缺失的情况下，这种传递在后来的后代中逐渐消失。一项降低 IMS Balb/c 小鼠的 acH4K12 水平的青少年治疗会加剧它们的情绪异常，但消除它们的认知缺陷。相反，进一步提高 acH4K12 水平的治疗改善了情绪表型，但对认知缺陷没有影响。此外，防止母亲出现情绪或认知缺陷的治疗也可以防止其后代出现此类缺陷，这表明早期生活压力的跨代影响是可以预防的。
Using a rodent paradigm of early life stress, infant maternal separation (IMS), we examined whether IMS-triggered behavioral and epigenetic phenotypes of the stress-susceptible mouse strain Balb/c are propagated across generations. These phenotypes include impaired emotional behavior and deficits in executive cognitive functions in adulthood, and they are associated with increased acetylation of histone H4K12 protein (acH4K12) in the forebrain neocortex. These behavioral and epigenetic phenotypes are transmitted to the first progeny of IMS Balb/c mothers, but not fathers, and cross-fostering experiments revealed that this transmission is triggered by maternal behavior and modulated by the genetic background of the pups. In the continued absence of the original stressor, this transmission fades in later progenies. An adolescent treatment that lowers the levels of acH4K12 in IMS Balb/c mice augments their emotional abnormality but abolishes their cognitive deficits. Conversely, a treatment that further elevates the levels of acH4K12 improved the emotional phenotype but had no effects on the cognitive deficits. Moreover, treatments that prevent the emergence of either emotional or cognitive deficits in the mother also prevent the establishment of such deficits in her offspring, indicating that trans-generational effects of early life stress can be prevented.
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影响因子：
3
作者：
Frederick AL;Saborido TP;Stanwood GD
通讯作者：
Stanwood GD
影响因子：
--
作者：
Green, Jennifer Greif;McLaughlin, Katie A.;Berglund, Patricia A.;Gruber, Michael J.;Sampson, Nancy A.;Zaslavsky, Alan M.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.
影响因子：
10.6
作者：
Roth, Tania L.;Lubin, Farah D.;Funk, Adam J.;Sweatt, J. David
通讯作者：
Sweatt, J. David
影响因子：
5.3
作者：
Bhansali, Punita;Dunning, Jane;Schmauss, Claudia
通讯作者：
Schmauss, Claudia
影响因子：
25
作者：
Weaver, ICG;Cervoni, N;Meaney, MJ
通讯作者：
Meaney, MJ