Working around the CLOCK: Cocaine-induced phase shift of NPAS2 and SIRT1 and their roles in directing drug-related behaviour (commentary on Becker-Krail et al., 2021).
Working around the CLOCK: Cocaine-induced phase shift of NPAS2 and SIRT1 and their roles in directing drug-related behaviour (commentary on Becker-Krail et al., 2021).
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围绕时钟工作：可卡因诱导的 NPAS2 和 SIRT1 相移及其在指导药物相关行为中的作用（Becker-Krail 等人的评论，2021）。
DOI：
10.1111/ejn.15464
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Smith,LauraN
中科院分区：
文献类型：
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作者：
Huebschman,JessicaL;Smith,LauraN
物质使用障碍（SUD）的神经生物学基础与昼夜节律和氧化还原代谢密切相关。滥用药物，如可卡因，破坏昼夜节律和氧化还原稳态，反过来，这些区域中的任一个的破坏影响药物相关行为（Hasler等人，2012; Uys等人，2014年）。虽然SUD和这两个系统之间的关系已经被独立研究，Becker-Krail及其同事（2021）在本期《欧洲神经科学杂志》上发表的研究是少数几项研究之一，研究了昼夜节律和代谢系统之间的直接分子相互作用如何调节药物相关行为。一段时间以来，转录因子神经元PAS结构域2（NPAS 2）和昼夜运动输出周期Kaput（CLOCK）是同源物，因此，尽管有些相似，但在两者中，NPAS 2通常处于次要地位。在哺乳动物中，CLOCK和NPAS 2都驱动昼夜节律基因（包括Period）的节律性转录，这反过来又在负反馈回路中抑制它们自己的转录，形成昼夜节律钟的基础（综述于Lowrey & Takahashi，2004）。虽然NPAS 2的作用最初在视交叉上核中没有被认识到，但后来的研究表明它的存在和能力，至少部分地，在这个大脑区域中也代表了CLOCK。
The underlying neurobiology of substance use disorders (SUDs) is closely entangled with that of both circadian rhythms and redox metabolism. Drugs of abuse, like cocaine, disrupt circadian rhythms and redox homeostasis, and in turn, disruption in either of these areas influences drug-related behaviors (Hasler et al., 2012; Uys et al., 2014). While the relationship between SUDs and these two systems have been investigated independently, the studies by Becker-Krail and colleagues (2021) in this issue of the European Journal of Neuroscience are among few examining how direct molecular interactions between circadian and metabolic systems may regulate drug-related behaviors.It has been clear for some time that the transcription factor Neuronal PAS Domain 2 (NPAS2) and Circadian Locomotor Output Cycles Kaput (CLOCK) are homologs, and thus, somewhat interchangeable—though, of the two, NPAS2 generally takes the back seat. In mammals, both CLOCK and NPAS2 drive the rhythmic transcription of circadian genes, including Period, which in turn inhibit their own transcription in a negative feedback loop, forming the basis of the circadian clock (reviewed in Lowrey & Takahashi, 2004). While NPAS2’s role was not originally recognized in the suprachiasmatic nucleus, the “master regulator” of circadian rhythmicity where CLOCK is predominant, later studies showed its presence and ability to, at least partially, stand-in for CLOCK in this brain region, as well.