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光周期对生物钟转录组可塑性的影响:雄性褪黑素敏感型小鼠的研究。

Transcriptomic Plasticity of the Circadian Clock in Response to Photoperiod: A Study in Male Melatonin-Competent Mice.

机构信息

Neuroscience Graduate Program, Vanderbilt University, Nashville, Tennessee.

Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee.

出版信息

J Biol Rhythms. 2024 Oct;39(5):423-439. doi: 10.1177/07487304241265439. Epub 2024 Aug 2.

DOI:10.1177/07487304241265439
PMID:39096022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11425976/
Abstract

Seasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus where it receives retinal input and synchronizes, or entrains, organismal physiology and behavior to the prevailing light cycle. The process of entrainment induces sustained plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood. Entrainment to different photoperiods persistently alters the timing, waveform, period, and light resetting properties of the SCN clock and its driven rhythms. To elucidate novel candidate genes for molecular mechanisms of photoperiod plasticity, we performed RNA sequencing on whole SCN dissected from mice raised in long (light:dark [LD] 16:8) and short (LD 8:16) photoperiods. Fewer rhythmic genes were detected in mice subjected to long photoperiod, and in general, the timing of gene expression rhythms was advanced 4-6 h. However, a few genes showed significant delays, including . There were significant changes in the expression of the clock-associated gene and in SCN genes related to light responses, neuropeptides, gamma aminobutyric acid (GABA), ion channels, and serotonin. Particularly striking were differences in the expression of the neuropeptide signaling genes and , as well as convergent regulation of the expression of 3 SCN light response genes, , , and . Transcriptional modulation of and and phase regulation of are compelling candidate molecular mechanisms for plasticity in the SCN light response through their modulation of the critical NMDAR-MAPK/ERK-CREB/CRE light signaling pathway in SCN neurons. Modulation of and may critically support SCN neural network reconfiguration during photoperiodic entrainment. Our findings identify the SCN light response and neuropeptide signaling gene sets as rich substrates for elucidating novel mechanisms of photoperiod plasticity. Data are also available at http://circadianphotoperiodseq.com/, where users can view the expression and rhythmic properties of genes across these photoperiod conditions.

摘要

季节性日长或昼夜节律光周期是一种普遍存在的环境信号,它深刻地影响着生理和行为。在哺乳动物中,中央生物钟位于下丘脑的视交叉上核(SCN)中,它接收视网膜输入并使机体的生理和行为与当前的光周期同步或重新同步。重新同步的过程会引起 SCN 的持续可塑性,但 SCN 可塑性的分子机制尚不完全清楚。适应不同的光周期会持续改变 SCN 时钟及其驱动节律的时间、波形、周期和光重置特性。为了阐明光周期可塑性的分子机制的新候选基因,我们对在长光照(LD 16:8)和短光照(LD 8:16)条件下饲养的小鼠的整个 SCN 进行了 RNA 测序。在长光照条件下饲养的小鼠中检测到的节律基因较少,并且一般来说,基因表达节律的时间提前了 4-6 小时。然而,一些基因显示出明显的延迟,包括 。与时钟相关的基因 和 SCN 中与光反应、神经肽、γ-氨基丁酸(GABA)、离子通道和血清素相关的基因表达都发生了显著变化。特别引人注目的是神经肽信号基因 和 的表达差异,以及 SCN 中 3 个光反应基因 、 、 的表达的趋同调节。 和 的转录调节以及 相位调节是 SCN 光反应可塑性的有吸引力的候选分子机制,因为它们通过调节 SCN 神经元中关键的 NMDAR-MAPK/ERK-CREB/CRE 光信号通路来调节 。 和 的调节可能对光周期适应过程中 SCN 神经网络的重新配置至关重要。我们的研究结果确定了 SCN 光反应和神经肽信号基因集作为阐明光周期可塑性新机制的丰富底物。这些数据也可以在 http://circadianphotoperiodseq.com/ 上获得,用户可以在这些光周期条件下查看基因的表达和节律特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/c68bdfa89f22/10.1177_07487304241265439-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/06a48371c249/10.1177_07487304241265439-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/28e3ede7609d/10.1177_07487304241265439-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/aa4b3e9b68ab/10.1177_07487304241265439-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/f5fd36a918a9/10.1177_07487304241265439-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/dce92570d3e0/10.1177_07487304241265439-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/94cbae81def8/10.1177_07487304241265439-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/c68bdfa89f22/10.1177_07487304241265439-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/06a48371c249/10.1177_07487304241265439-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/28e3ede7609d/10.1177_07487304241265439-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/aa4b3e9b68ab/10.1177_07487304241265439-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/f5fd36a918a9/10.1177_07487304241265439-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/dce92570d3e0/10.1177_07487304241265439-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/94cbae81def8/10.1177_07487304241265439-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7d/11425976/c68bdfa89f22/10.1177_07487304241265439-fig7.jpg

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