Nuclear Arc Puts a Brake on Cocaine-Induced Chromatin Remodeling and Behaviors.
Nuclear Arc Puts a Brake on Cocaine-Induced Chromatin Remodeling and Behaviors.
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核电弧抑制可卡因诱导的染色质重塑和行为。
DOI：
10.1016/j.biopsych.2017.01.007
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发表时间：
2017
影响因子：
10.6
通讯作者：
Lobo,MaryKay
中科院分区：
文献类型：
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作者：
Lobo,MaryKay
包括可卡因在内的精神兴奋剂会导致神经元细胞核中的分子适应，包括染色质重塑和基因转录改变(1)。这些分子适应在细胞和电路水平上具有深远的影响，并最终影响行为输出(1)。大量研究表明，在反复或急性可卡因暴露后，包括纹状体在内的大脑奖励区域的转录和染色质重塑发生了改变（1-4）。虽然对暴露于可卡因后染色质重塑及其对基因转录的影响进行了大量研究，但对染色质组织改变的机制知之甚少。在本期的《生物精神病学》中，Salery等人(5)通过研究纹状体核积累的活性调节细胞骨架相关蛋白（Arc）在可卡因暴露后染色质重塑和行为中的作用，对此提供了新的见解。大量研究将Arc确定为一种即时早期基因（IEG），这是一组在受到刺激（如可卡因）后立即被短暂诱导的基因。与c-Fos和FosB等转录因子相比，Arc属于改变细胞过程的效应蛋白eggs(2)。电弧在树突隔室中积累，导致突触过程改变(6)。然而，有证据表明在核中存在弧的积累，并且弧包含控制其核积累的区域，包括核定位信号、核保留域和核输出信号(7)。Arc在细胞核中的功能尚不清楚，因为它已被证明对转录具有允许和抑制作用（7,8）。此外，尽管可卡因暴露后纹状体中诱导了Arc(2)，但可卡因暴露后纹状体神经元中Arc的作用尚未得到很好的研究。Salery等(5)在本期中提供了Arc在可卡因暴露后纹状体神经元核中的新的机制作用的数据。
Psychostimulants, including cocaine, cause molecular adaptations in the nucleus of neurons, which include chromatin remodeling and altered gene transcription (1). These molecular adaptations have profound effects at the levels of the cell and circuitry, and ultimately in behavioral output (1). Numerous studies demonstrate altered transcription and chromatin remodeling in brain reward regions, including the striatum, after repeated or acute cocaine exposure (1–4). While there has been much investigation into chromatin remodeling and its effects on gene transcription after exposure to cocaine, there is minimal information into the mechanisms that underlie the alterations in chromatin organization. In this issue of Biological Psychiatry, Salery et al.(5) provide new insight into this by examining a role for striatal nuclear accumulation of activity-regulated cytoskeleton-associated protein (Arc) on chromatin remodeling, as well as behavior, in response to cocaine exposure.Numerous studies identify Arc as an immediate early gene (IEG), a set of genes that are transiently induced immediately after a stimulus, such as cocaine. Arc belongs to the group of effector protein IEGs that alter cellular processes in contrast to transcription factor IEGs, such as c-Fos and FosB (2). Arc accumulates in dendritic compartments, resulting in altered synaptic processes (6). However, there is evidence for Arc accumulation in the nucleus, and Arc contains regions that control its nuclear accumulation, including a nuclear localization signal, a nuclear retention domain, and a nuclear export signal (7). The function of Arc in the nucleus is unclear, as it has been demonstrated to have both a permissive and a repressive role on transcription (7, 8). Further, although Arc is induced in striatum after cocaine exposure (2), the role of Arc in striatal neurons after cocaine is not well studied. In this issue, Salery et al.(5) provide data for a new mechanistic role of Arc in striatal neuron nuclei after cocaine exposure.