Retardation of neurobehavioral development and reelin down-regulation regulated by further DNA methylation in the hippocampus of the rat pups are associated with maternal deprivation
Retardation of neurobehavioral development and reelin down-regulation regulated by further DNA methylation in the hippocampus of the rat pups are associated with maternal deprivation
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DOI：
10.1016/j.bbr.2010.10.018
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发表时间：
2011-02
影响因子：
2.7
通讯作者：
Lina Qin;Wen-qiang Tu;Xiumin Sun;Jianlong Zhang;Yuchuang Chen;Hu Zhao
中科院分区：
文献类型：
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作者：
Lina Qin;Wen-qiang Tu;Xiumin Sun;Jianlong Zhang;Yuchuang Chen;Hu Zhao
众所周知，早期生活应激对早期发育的海马体有深远的影响。Reelin是一种在胚胎发育过程中调节神经元迁移的大型蛋白质。Reelin在大脑中持续表达，但其功能鲜为人知。本研究旨在探讨母体剥夺(MD)对大鼠早期神经行为发育的影响，以及Reelin在海马区的作用及其可能的调控机制。在出生后2-15天(PND)从母亲身边取出幼鼠，每天3小时。在前3周测试包括抓握、步态、扶正、回避悬崖、听觉惊吓、热板试验和负向趋地性在内的反射发展。采用实时荧光定量聚合酶链式反应(Real-Time-PCR)技术检测大鼠海马区reelin基因甲基化水平。正如预期的那样，在大鼠幼崽的神经行为和reelin表达方面出现了一些差异。马立克氏病大鼠在体重、听觉惊厥和抓握反射方面存在明显不足，而在热板试验中表现出明显的增强。在PND 22时，海马区的Reelin mRNA表达减少，随后是MD。同时，DNA甲基化的变化与reelin的表达呈现相反的趋势。这些结果表明，早期MD对神经行为发育有不良影响，并通过进一步的DNA甲基化导致出生后海马区reelin基因表达下调。
It is known that early life stress has profound effects in early developing hippocampus. Reelin is a large protein that regulates neuronal migration during embryonic development. The expression of reelin persists in brain, but its function is little known. The aim of the present study was to investigate the effects of maternal deprivation (MD) on early neurobehavioral development of rats, and the role of reelin and the potential mechanism underlying regulation of its expression in hippocampus. Rat pups were removed from mothers during the postnatal day (PND) 2–15 for 3h a day. Reflex developments including grasping, gait, righting, cliff avoidance, auditory startle, hot-plate test and negative geotaxis, were tested during the first 3 weeks. The level of reelin mRNA and reelin gene methylation in the hippocampal formation were determined using real-time PCR analysis. As expected, some differences appeared in the measure of neurobehavior and expression of reelin in rat pups. Several significant deficiencies were observed in bodyweight, auditory startle and grasping reflex while a great enhancement in hot-plate test in rat pups suffering from MD. On PND 22, the expression of reelin mRNA reduced in the hippocampus followed by MD. Meanwhile, the changes of DNA methylation showed an opposite trend compared with the reelin expression. The results suggest that MD in early life has harmful effects on neurobehavioral development, and causes the down-regulation of reelin mRNA by further DNA methylation in postnatal hippocampus.