日本筑波大学Yu Hayashi团队近期取得重要工作进展，他们研究发现，对快速眼动睡眠至关重要的脑桥-髓质回路缺失与帕金森疾病相关。相关研究成果2024年9月19日在线发表于《细胞》杂志上。

据介绍，由于脑干的神经元异质性，识别快速眼动（REM）睡眠回路的特性及其与疾病的关系一直具有挑战性。

研究人员在小鼠中发现，脑桥嗅觉下被盖（SubLDT）中的神经元表达，促肾上腺皮质激素释放激素结合蛋白（Crhbp⁺神经元）并投射到髓质，促进REM睡眠。

在接受Crhbp⁺神经元投射的髓质区域内，表达一氧化氮合酶1的神经元（Nos1⁺神经元）投射到SubLDT并促进REM睡眠，这表明桥脑和髓质之间存在一个正相互作用的回路，作为核心REM睡眠回路。Nos1⁺神经元也投射到控制广泛前脑活动的区域。

清除Crhbp⁺神经元会减少睡眠并损害REM睡眠张力。在患有REM睡眠行为障碍的帕金森病患者中，CRHBP免疫反应神经元大量减少，并含有病理性α-突触核蛋白，这为深入了解该疾病睡眠缺陷的机制提供了线索。

附：英文原文

Title: A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson’s disease

Author: Mitsuaki Kashiwagi, Goichi Beck, Mika Kanuka, Yoshifumi Arai, Kaeko Tanaka, Chika Tatsuzawa, Yumiko Koga, Yuki C. Saito, Marina Takagi, Yo Oishi, Masanori Sakaguchi, Kousuke Baba, Masashi Ikuno, Hodaka Yamakado, Ryosuke Takahashi, Masashi Yanagisawa, Shigeo Murayama, Takeshi Sakurai, Kazuya Sakai, Yoshimi Nakagawa, Masahiko Watanabe, Hideki Mochizuki, Yu Hayashi

Issue&Volume: 2024-09-19

Abstract: Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp+ neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp+ neurons, neurons expressing nitric oxide synthase 1 (Nos1+ neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1+ neurons also project to areas that control wide forebrain activity. Ablating Crhbp+ neurons reduces sleep and impairs REM sleep atonia. In Parkinson’s disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic α-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease.

DOI: 10.1016/j.cell.2024.08.046

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00975-9