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表观遗传学及其对行为神经内分泌学的影响。

Epigenetics and its implications for behavioral neuroendocrinology.

作者信息

Crews David

机构信息

Section of Integrative Biology and Center of Behavioral Neuroendocrinology, University of Texas at Austin, Austin, TX 78712, USA.

出版信息

Front Neuroendocrinol. 2008 Jun;29(3):344-57. doi: 10.1016/j.yfrne.2008.01.003. Epub 2008 Feb 7.

Abstract

Individuals vary in their sociosexual behaviors and reactivity. How the organism interacts with the environment to produce this variation has been a focus in psychology since its inception as a scientific discipline. There is now no question that cumulative experiences throughout life history interact with genetic predispositions to shape the individual's behavior. Recent evidence suggests that events in past generations may also influence how an individual responds to events in their own life history. Epigenetics is the study of how the environment can affect the genome of the individual during its development as well as the development of its descendants, all without changing the DNA sequence. Several distinctions must be made if this research is to become a staple in behavioral neuroendocrinology. The first distinction concerns perspective, and the need to distinguish and appreciate, the differences between Molecular versus Molar epigenetics. Each has its own lineage of investigation, yet both appear to be unaware of one another. Second, it is important to distinguish the difference between Context-Dependent versus Germline-Dependent epigenetic modifications. In essence the difference is one of the mechanism of heritability or transmission within, as apposed to across, generations. This review illustrates these distinctions while describing several rodent models that have shown particular promise for unraveling the contribution of genetics and the environment on sociosexual behavior. The first focuses on genetically-modified mice and makes the point that the early litter environment alters subsequent brain activity and behavior. This work emphasizes the need to understand behavioral development when doing research with such animals. The second focuses on a new rat model in which the epigenome is permanently imprinted, an effect that crosses generations to impact the descendants without further exposure to the precipitating agent. This work raises the question of how events in generations past can have consequences at both the mechanistic, behavioral, and ultimately evolutionary levels.

摘要

个体在其社会性行为和反应性方面存在差异。自心理学成为一门科学学科以来,生物体如何与环境相互作用以产生这种差异一直是心理学的一个焦点。现在毫无疑问,贯穿生命历程的累积经历与遗传倾向相互作用,塑造了个体的行为。最近的证据表明,过去几代人的事件也可能影响个体对自己生命历程中事件的反应方式。表观遗传学是研究环境如何在个体及其后代的发育过程中影响基因组,而不改变DNA序列。如果这项研究要成为行为神经内分泌学的主要内容,就必须做出几个区分。第一个区分涉及视角,以及区分和认识分子表观遗传学与整体表观遗传学之间的差异的必要性。它们各自有自己的研究脉络,但似乎彼此都没有意识到对方。其次,区分上下文依赖型与种系依赖型表观遗传修饰之间的差异很重要。本质上,这种差异是遗传或跨代传递机制的差异。这篇综述阐述了这些区分,同时描述了几种啮齿动物模型,这些模型在揭示基因和环境对社会性行为的贡献方面显示出了特别的前景。第一个模型聚焦于基因改造小鼠,并指出早期窝仔环境会改变随后的大脑活动和行为。这项工作强调了在用此类动物进行研究时理解行为发展的必要性。第二个模型聚焦于一种新的大鼠模型,其中表观基因组被永久印记,这种效应会跨代影响后代,而无需进一步接触引发因素。这项工作提出了一个问题,即过去几代人的事件如何在机制、行为以及最终的进化层面产生影响。

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