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从电路到染色质:表观遗传学在心理健康中的新兴作用。

From Circuits to Chromatin: The Emerging Role of Epigenetics in Mental Health.

机构信息

Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10129

Departments of Pharmacology, Molecular Physiology and Biophysics, Psychiatry and Behavioral Sciences; Vanderbilt Center for Addiction Research; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee 37323.

出版信息

J Neurosci. 2021 Feb 3;41(5):873-882. doi: 10.1523/JNEUROSCI.1649-20.2020. Epub 2021 Jan 14.

Abstract

A central goal of neuroscience research is to understand how experiences modify brain circuits to guide future adaptive behavior. In response to environmental stimuli, neural circuit activity engages gene regulatory mechanisms within each cell. This activity-dependent gene expression is governed, in part, by epigenetic processes that can produce persistent changes in both neural circuits and the epigenome itself. The complex interplay between circuit activity and neuronal gene regulation is vital to learning and memory, and, when disrupted, is linked to debilitating psychiatric conditions, such as substance use disorder. To develop clinical treatments, it is paramount to advance our understanding of how neural circuits and the epigenome cooperate to produce behavioral adaptation. Here, we discuss how new genetic tools, used to manipulate neural circuits and chromatin, have enabled the discovery of epigenetic processes that bring about long-lasting changes in behavior relevant to mental health and disease.

摘要

神经科学研究的一个核心目标是了解经验如何改变大脑回路,以指导未来的适应性行为。针对环境刺激,神经回路活动会在每个细胞内激活基因调控机制。这种活性依赖的基因表达部分受表观遗传过程的控制,这些过程可以在神经回路和表观基因组本身中产生持久的变化。回路活动和神经元基因调控之间的复杂相互作用对学习和记忆至关重要,而当这种相互作用被打乱时,就会导致精神疾病,如物质使用障碍等。为了开发临床治疗方法,至关重要的是要加深我们对神经回路和表观基因组如何合作产生行为适应的理解。在这里,我们讨论了新的遗传工具如何用于操纵神经回路和染色质,从而发现与心理健康和疾病相关的具有持久行为改变的表观遗传过程。

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