Early Environments, Glucocorticoid Receptors, and Behavioral Epigenetics
Early Environments, Glucocorticoid Receptors, and Behavioral Epigenetics
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DOI：
10.1037/a0034186
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发表时间：
2013-10-01
影响因子：
1.9
通讯作者：
Champagne, Frances A.
中科院分区：
文献类型：
--
作者：
Champagne, Frances A.
1985年，《行为神经科学》（Behavioral Neuroscience）杂志发表了一篇简短的报告，建立了新生大鼠的处理与成年大鼠海马糖皮质激素受体（GR）浓度之间的联系，表明处理与非处理后代中观察到的应激反应减弱的神经生物学基础。为了庆祝行为神经科学30周年，本文探讨了这篇简短但重要的出版物之前和之后的研究。处理引起的海马GR的变化被确定为涉及甲状腺激素、5-羟色胺周转和转录因子与Nr 3c 1基因结合的一系列细胞和分子事件的结果，导致GR mRNA和蛋白质增加。虽然提出了许多假设的“处理效果”，处理引起的变化，在孕产妇保健，特别是小狗舔/理毛（LG）的作用，产生了一个富有成效的科学框架，了解处理现象。事实上，LG已经被证明可以通过所描述的处理信号通路改变GR水平。此外，已发现表观遗传机制在早期生活经验的影响中起着关键作用，特别是在Nr 3c 1的调节中。总的来说，从最初发现处理引起的GR变化演变而来的研究途径对我们理解可塑性、弹性和性状的代际传递具有广泛的应用。
In 1985, a brief report published in Behavioral Neuroscience established the link between neonatal handling and concentrations of hippocampal glucocorticoid receptors (GR) in the adult rat, suggesting a neurobiological basis for the attenuated stress reactivity observed in handled versus nonhandled offspring. To celebrate the 30th anniversary of Behavioral Neuroscience, this article explores the research that preceded and followed from this brief but significant publication. Changes in hippocampal GR induced by handling were determined to be the outcome of a cascade of cellular and molecular events involving thyroid hormones, serotonin turnover, and transcription factor binding to the Nr3c1 gene, leading to increased GR mRNA and protein. Though many hypotheses were proposed for the "handling effect," the role of handling-induced changes in maternal care, particularly pup licking/grooming (LG), generated a productive scientific framework for understanding the handling phenomenon. Indeed, LG has since been demonstrated to alter GR levels through the signaling pathways described for handling. Moreover, epigenetic mechanisms have been discovered to play a critical role in the effects of early life experience and particularly in the regulation of Nr3c1. Overall, the research avenues that have evolved from the initial finding of handling-induced changes in GR have broad applications to our understanding of plasticity, resilience, and the transmission of traits across generations.