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向中缝核微量注射促黑素(MCH)可促进大鼠的快速眼动睡眠。

Microinjection of melanin-concentrating hormone (MCH) into the median raphe nucleus promotes REM sleep in rats.

作者信息

Pascovich Claudia, Niño Sofia, Mondino Alejandra, Lopez-Hill Ximena, Urbanavicius Jessika, Monti Jaime, Lagos Patricia, Torterolo Pablo

机构信息

Facultad de Medicina, Universidad de la República, Fisiología, Montevideo - Uruguay.

Instituto de Investigaciones Biológicas Clemente Estable, Neurofarmacología Experimental, Montevideo - Uruguay.

出版信息

Sleep Sci. 2021 Jul-Sep;14(3):229-235. doi: 10.5935/1984-0063.20200075.

DOI:10.5935/1984-0063.20200075
PMID:35186201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8848522/
Abstract

Melanin concentrating hormone (MCH) is a sleep-promoting neuromodulator synthesized by neurons located in the postero-lateral hypothalamus and incerto-hypothalamic area. MCHergic neurons have widespread projections including the serotonergic dorsal (DR) and median (MnR) raphe nuclei, both involved in the control of wakefulness and sleep. In the present study, we explored in rats the presence of the MCH receptor type 1 (MCHR-1) in serotonergic neurons of the MnR by double immunofluorescence. Additionally, we analyzed the effect on sleep of MCH microinjections into the MnR. We found that MCHR-1 protein was present in MnR serotonergic and non-serotonergic neurons. In this respect, the receptor was localized in the primary cilia of these neurons. Compared with saline, microinjections of MCH into the MnR induced a dose-related increase in REM sleep time, which was related to a rise in the number of REM sleep episodes, associated with a reduction in the time spent in W. No significant changes were observed in non-REM (NREM) sleep time. Our data strongly suggest that MCH projections towards the MnR, acting through the MCHR-1 located in the primary cilia, promote REM sleep.

摘要

黑色素聚集激素(MCH)是一种促进睡眠的神经调质,由位于下丘脑后外侧和下丘脑未定带区域的神经元合成。MCH能神经元具有广泛的投射,包括参与觉醒和睡眠控制的5-羟色胺能背侧(DR)和中缝(MnR)中缝核。在本研究中,我们通过双重免疫荧光法在大鼠中探索了MnR的5-羟色胺能神经元中1型MCH受体(MCHR-1)的存在情况。此外,我们分析了向MnR微量注射MCH对睡眠的影响。我们发现MCHR-1蛋白存在于MnR的5-羟色胺能和非5-羟色胺能神经元中。在这方面,该受体定位于这些神经元的初级纤毛中。与生理盐水相比,向MnR微量注射MCH可导致快速眼动(REM)睡眠时间呈剂量相关增加,这与REM睡眠发作次数增加有关,同时清醒(W)时间减少。非快速眼动(NREM)睡眠时间未观察到显著变化。我们的数据强烈表明,MCH向MnR的投射通过位于初级纤毛中的MCHR-1发挥作用,促进REM睡眠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/7e68d56e88f8/ssci-14-03-0229-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/c4b22ee5374a/ssci-14-03-0229-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/24b611d7fb5c/ssci-14-03-0229-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/b577cf984a8d/ssci-14-03-0229-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/7e68d56e88f8/ssci-14-03-0229-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/c4b22ee5374a/ssci-14-03-0229-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/24b611d7fb5c/ssci-14-03-0229-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/b577cf984a8d/ssci-14-03-0229-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9051/8848522/7e68d56e88f8/ssci-14-03-0229-g04.jpg

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Peptides. 2020 Apr;126:170249. doi: 10.1016/j.peptides.2019.170249. Epub 2020 Jan 3.
2
REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories.快速眼动睡眠(REM)活跃的促黑素细胞皮质素(MCH)神经元参与遗忘海马依赖性记忆。
Science. 2019 Sep 20;365(6459):1308-1313. doi: 10.1126/science.aax9238.
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Melanin-concentrating hormone receptor-1 is located in primary cilia of the dorsal raphe neurons.
Front Physiol. 2023 Jan 17;13:1099276. doi: 10.3389/fphys.2022.1099276. eCollection 2022.
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The melanin-concentrating hormone system as a target for the treatment of sleep disorders.作为睡眠障碍治疗靶点的促黑素细胞激素系统。
Front Neurosci. 2022 Sep 13;16:952275. doi: 10.3389/fnins.2022.952275. eCollection 2022.
黑皮质素受体 1 位于中缝背核神经元的初级纤毛内。
J Chem Neuroanat. 2019 Jul;98:55-62. doi: 10.1016/j.jchemneu.2019.03.003. Epub 2019 Mar 31.
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Distribution of MCH-containing fibers in the feline brainstem: Relevance for REM sleep regulation.猫脑干内含 MCH 的纤维分布:与 REM 睡眠调节的关系。
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Melanin-concentrating hormone-expressing neurons adjust slow-wave sleep dynamics to catalyze paradoxical (REM) sleep.表达黑色素聚集激素的神经元调节慢波睡眠动力学以促进反常(REM)睡眠。
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