Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Behav Brain Res. 2011 Feb 2;217(1):142-7. doi: 10.1016/j.bbr.2010.10.018. Epub 2010 Oct 23.
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.
已知早期生活压力对早期发育的海马体有深远影响。 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 的表达在大脑中持续存在，但它的功能知之甚少。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 的作用及其在海马体中表达调控的潜在机制。在产后第 2-15 天期间，每天将幼鼠从母亲身边移走 3 小时。在头 3 周内，测试了抓握、步态、翻身、悬崖回避、听觉惊跳、热板测试和负趋地性等反射发育。使用实时 PCR 分析确定海马体形成中 Reelin mRNA 和 Reelin 基因甲基化的水平。正如预期的那样，在神经行为和 Reelin 表达的测量中出现了一些差异。在 MD 大鼠幼仔中，体重、听觉惊跳和抓握反射等方面存在明显缺陷，而热板测试则显著增强。在 PND 22 时，海马体中 Reelin mRNA 的表达减少，随后是 MD。同时，DNA 甲基化的变化与 Reelin 表达呈现相反的趋势。结果表明，早期生活中的 MD 对神经行为发育有不良影响，并通过产后海马体中的进一步 DNA 甲基化导致 Reelin mRNA 的下调。
