Orexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity.

IF 6.9 1区 生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-02-25 Epub Date: 2025-02-12 DOI:10.1016/j.celrep.2025.115277
Shuntaro Izawa, Debora Fusca, Hong Jiang, Christian Heilinger, A Christine Hausen, F Thomas Wunderlich, Lukas Steuernagel, Peter Kloppenburg, Jens C Brüning
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Abstract

Orexin/hypocretin receptor type 2 (Ox2R), which is widely expressed in the brain, receives orexin signals and modulates sleep and metabolism. Ox2R selective agonists are currently under clinical trials for narcolepsy treatment. Here, we focused on Ox2R expression and function in melanin-concentrating hormone (MCH) neurons, which have opposite roles to orexin neurons in sleep and metabolism regulation. Ox2R-expressing MCH neurons showed heterogeneity of RNA expression, and orexin B application in brain slices induced both excitatory and inhibitory responses in distinct MCH neuron populations. Ox2R inactivation in MCH neurons reduced transitions from non-rapid eye movement (NREM) to REM sleep and impaired insulin sensitivity with excessive feeding after a fasting period in female mice. In conclusion, Ox2R mediates excitatory and inhibitory responses in MCH neuron sub-populations in vivo, which regulate sleep and metabolism in female mice.

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MCH神经元中食欲素/下丘脑分泌素受体2信号调节REM睡眠和胰岛素敏感性。
食欲素/下丘脑分泌素受体2型(Ox2R)在大脑中广泛表达,接收食欲素信号并调节睡眠和代谢。Ox2R选择性激动剂目前正处于治疗发作性睡病的临床试验中。在这里,我们重点研究了Ox2R在黑色素集中激素(MCH)神经元中的表达和功能,这些神经元在睡眠和代谢调节中与食欲素神经元具有相反的作用。表达ox2r的MCH神经元表现出RNA表达的异质性,在脑切片中应用食欲素B可诱导不同MCH神经元群体的兴奋性和抑制性反应。雌性小鼠的MCH神经元Ox2R失活减少了从非快速眼动(NREM)到快速眼动(REM)睡眠的转变,并在禁食期后过度进食损害了胰岛素敏感性。综上所述,在体内,Ox2R介导MCH神经元亚群的兴奋和抑制反应,调节雌性小鼠的睡眠和代谢。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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