Litter and sex effects on maternal behavior and DNA methylation of the Nr3c1 exon 17 promoter gene in hippocampus and cerebellum.

Litter and sex effects on maternal behavior and DNA methylation of the Nr3c1 exon 17 promoter gene in hippocampus and cerebellum.
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DOI:
10.1016/j.ijdevneu.2014.03.010
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发表时间:
2014-08
期刊:
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
影响因子:
--
通讯作者:
Nielsen DA
Nielsen DA
中科院分区:
其他
文献类型:
--
作者:
Kosten TA;Nielsen DA

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早期生活事件可以通过DNA甲基化改变基因表达。海马糖皮质激素受体(NR3C1基因)外显子17启动子的甲基化状态与幼犬舔食频率有关。这项工作的大部分都是在雄性老鼠身上进行的。因为母鸭更频繁地舔雄性幼崽,这可能通过DNA甲基化导致表型上的性别差异。修改胎仔性别组成(LGC)改变了母亲的行为。在LGC中,将单性猫咪的后代与混合性别猫咪的后代进行比较。此前,我们证明了LGC和性别影响幼崽的舔食次数,以及青春期焦虑和海马区NR3C1外显子17启动子基因的DNA甲基化。现在,我们通过检查对小脑的影响和测量信使核糖核酸水平来扩展这项工作。我们还使用焦磷酸测序法重新评估了海马区的DNA甲基化,并使用更常用的频率测量方法重新分析了幼犬舔食。在出生后第1天(PN1)被扑杀到8只幼崽,被分配到三种情况之一:全雄性(n=10),全雌性(n=12),或男女各一半(n=20)。在PN4、PN7和PN10上进行舔食评分。在PN35上采集海马区和小脑样本。单一性别的男性被舔的最少,混血的男性最多。在DNA甲基化中没有LGC或性别效应的混合雌性大鼠海马区NR3C1mRNA水平最低。混合男性的小脑DNA甲基化水平最低,对信使核糖核酸水平没有影响。母犬舔食与小脑和海马区NR3C117外显子启动基因的DNA甲基化有关。
Early life events can alter gene expression through DNA methylation. The methylation status of the exon 17 promoter of the glucocorticoid receptor (Nr3c1 gene) in hippocampus associates with frequency of pup licking. Much of this work was conducted with male rats. Because dams more frequently lick male pups, this may contribute to sex differences in phenotypes through DNA methylation. Modifying litter gender composition (LGC), in which offspring of single-sex litters are compared to mixed-sex litters, alters maternal behavior. Previously, we demonstrated that LGC and sex affected pup licking times as well as anxiety and hippocampal DNA methylation of the Nr3c1 exon 17 promoter gene in adolescence. Now, we expand upon this work by examining effects in cerebellum and measuring mRNA levels. We also re-assessed DNA methylation in hippocampus using pyrosequencing and re-analyzed pup licking with the more commonly used frequency measure. Litters, culled to 8 pups on postnatal day 1 (PN1), were assigned to one of three conditions: all male, (n=10), all female, (n=12), or half of each sex (n=20). Licking was rated on PN4, 7, and 10. On PN35, hippocampal and cerebellar samples were obtained. Single-sex males were licked the least and mixed-sex males, the most. Hippocampal Nr3c1 mRNA levels were lowest in mixed females with no LGC or Sex effects in DNA methylation. Cerebellar DNA methylation levels were lowest in mixed males with no effect on mRNA levels. Maternal pup licking associated with DNA methylation of the Nr3c1 exon 17 promoter gene in cerebellum and with hippocampal mRNA.
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