脉络丛中的昼夜节律钟在上丘脑核的控制下驱动多个细胞过程的节律。

IF 5.9 1区 医学 Q1 NEUROSCIENCES
Martin Sládek, Pavel Houdek, Jihwan Myung, Kateryna Semenovykh, Tereza Dočkal, Alena Sumová
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引用次数: 0

摘要

脉络丛(Choroid plexus,ChP)是主要负责产生脑脊液的大脑结构,包含一个强大的昼夜节律时钟,其作用仍有待阐明。我们研究的目的是:[1] 确定小鼠脉络丛中受节律控制的细胞过程;[2] 评估来自控制脉络丛节律的蛛网膜上核(SCN)主时钟信号的作用和性质。为了实现这一目标,我们使用了多种小鼠模型(WT、mPer2Luc、ChP 特异性 Bmal1 基因敲除),并结合了多种实验方法,包括手术切除 SCN(SCNx)、时间分辨转录组学和单细胞发光显微镜。我们发现,在对照组(Ctrl)小鼠的ChP中,在黑暗中每4小时收集2个昼夜节律周期的ChP,ChP时钟调控许多过程,包括脑脊液昼夜节律分泌组、内质网应激反应的精确时间,以及控制涉及神经退行性疾病(阿尔茨海默病、亨廷顿氏病和额颞叶痴呆症)的基因。在 SCNx 小鼠的 ChP 中,体内和体外检测到的节律性被严重抑制,其程度与 ChP 特异性 Bmal1 基因敲除的小鼠相当。我们的数据表明,ChP 时钟控制组织特异性基因表达,并强烈依赖于与 SCN 的功能性连接。这些结果可能有助于寻找 ChP 时钟紊乱与大脑健康受损之间的新联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The circadian clock in the choroid plexus drives rhythms in multiple cellular processes under the control of the suprachiasmatic nucleus.

Choroid plexus (ChP), the brain structure primarily responsible for cerebrospinal fluid production, contains a robust circadian clock, whose role remains to be elucidated. The aim of our study was to [1] identify rhythmically controlled cellular processes in the mouse ChP and [2] assess the role and nature of signals derived from the master clock in the suprachiasmatic nuclei (SCN) that control ChP rhythms. To accomplish this goal, we used various mouse models (WT, mPer2Luc, ChP-specific Bmal1 knockout) and combined multiple experimental approaches, including surgical lesion of the SCN (SCNx), time-resolved transcriptomics, and single cell luminescence microscopy. In ChP of control (Ctrl) mice collected every 4 h over 2 circadian cycles in darkness, we found that the ChP clock regulates many processes, including the cerebrospinal fluid circadian secretome, precisely times endoplasmic reticulum stress response, and controls genes involved in neurodegenerative diseases (Alzheimer's disease, Huntington's disease, and frontotemporal dementia). In ChP of SCNx mice, the rhythmicity detected in vivo and ex vivo was severely dampened to a comparable extent as in mice with ChP-specific Bmal1 knockout, and the dampened cellular rhythms were restored by daily injections of dexamethasone in mice. Our data demonstrate that the ChP clock controls tissue-specific gene expression and is strongly dependent on the presence of a functional connection with the SCN. The results may contribute to the search for a novel link between ChP clock disruption and impaired brain health.

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来源期刊
Fluids and Barriers of the CNS
Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience
CiteScore
10.70
自引率
8.20%
发文量
94
审稿时长
14 weeks
期刊介绍: "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).
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