Understanding the mechanism of sleepiness by exploring mesolimbic glia-neuron interactions

通过探索中脑边缘胶质神经元相互作用来了解嗜睡的机制

• 批准号: 21H02802
• 负责人: ラザルス ミハエル
• 金额: $ 10.9万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21H02802/
• 关键词: Sleep; Glia; scRNAseq; sleep; glia

We previously developed the first positive allosteric modulator of adenosine A2A receptors (A2AR), named A2AR PAM-1, that evokes A2AR responses in the brain (e.g., sleep induction) without affecting cardiovascular function, unlike classic A2AR agonists. We are now collaborating with the Abe Lab (Hiroshima University, Graduate School of Advanced Science and Engineering) to develop a visible-light (420 nm) photoactivatable (‘caged’) A2AR PAM-1. Using the opto-version of the A2AR PAM, we, for the first time, optochemically induced sleep in freely behaving mice and demonstrated that extracellular adenosine produced by glia and neurons in nucleus accumbens promotes sleep [Roy K et al., in preparation].

我们先前开发了腺苷A2 A受体（A2 AR）的第一个正变构调节剂，命名为A2 AR PAM-1，其在脑中引起A2 AR反应（例如，睡眠诱导），而不影响心血管功能，不像经典的A2 AR激动剂。我们现在正在与安倍实验室（广岛大学，高等科学与工程研究科）合作开发可见光（420 nm）光活化（“笼”）A2 AR PAM-1。使用A2 AR PAM的光学版本，我们首次在自由行为的小鼠中光化学诱导睡眠，并证明由神经胶质细胞和神经元在丘脑核中产生的细胞外腺苷促进睡眠[Roy K et al.，正在编写中]。

项目成果

Principles and Practice of Sleep Medicine (Seventh Edition)

睡眠医学原理与实践（第七版）

• 发表时间: 2022
• 作者: Lazarus Michael;Oishi Yo;Landolt Hans Peter
• 通讯作者: Landolt Hans Peter

Mesencephalic dopamine neurons are essential for modafinil‐induced arousal

• DOI: 10.1111/bph.15660
• 发表时间: 2021-08
• 期刊: British Journal of Pharmacology
• 影响因子: 7.3
• 作者: Yan-fei Yang;Hui Dong;Yan Shen;Lei Li;M. Lazarus;W. Qu;Zhi-Li Huang

The gating of sleep homeostasis by motivation. Why are we sleepy when bored?

通过动机控制睡眠稳态。

• 发表时间: 2021
• 作者: Kondo T;Hara N;Koyama S;Yada Y;Tsukita K;Nagahashi A;Ikeuchi T;Ishii K;Asada T;Arai T;Yamada R;Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI);Alzheimer’s Disease Neuroimaging Initiative (ADNI);Inoue H;Reona Yamaguchi;Sasaki R.;Lazarus Michael
• 通讯作者: Lazarus Michael