Adenosine A(2A) receptors in the olfactory bulb suppress rapid eye movement sleep in rodents
Adenosine A(2A) receptors in the olfactory bulb suppress rapid eye movement sleep in rodents
复制标题
嗅球中的腺苷 A2A 受体抑制啮齿类动物的快速眼动睡眠。
DOI：
10.1007/s00429-016-1281-2
复制
发表时间：
2017
影响因子：
3.1
通讯作者：
Huang Zhi-Li
中科院分区：
文献类型：
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作者：
Wang Yi-Qun;Li Rui;Wang Dian-Ru;Cherasse Yoan;Zhang Ze;Zhang Meng-Qi;Lavielle Oriana;McEown Kristopher;Schiffmann Serge N.;d'Exaerde Alban de Kerchove;Qu Wei-Min;Lazarus Michael;Huang Zhi-Li
人类的快速眼动(REM)睡眠行为障碍通常伴随着嗅觉和嗅觉能力的降低，而去嗅球的大鼠表现出更多的REM睡眠，这表明嗅球(OB)参与了REM睡眠调节。然而，OB调节REM睡眠的分子机制尚不清楚。腺苷促进睡眠，其A2A型受体(A2AR)在卵巢中表达。我们假设OB中的A2AR调节快速眼动睡眠。大鼠双侧OB区微量注射A2AR拮抗剂SCH58261可增加REM睡眠，而微量注射A2AR激动剂CGS21680则减少REM睡眠。与A2AR拮抗剂类似，携带A2AR短发夹状RNA的腺相关病毒选择性地敲除大鼠OB中的A2AR可增加REM睡眠。基于设计者受体的化学遗传学，我们证明了抑制A2AR神经元可以增加REM睡眠，而激活这些神经元则会减少REM睡眠。此外，采用条件性顺行轴索追踪方法，我们发现OB A2AR神经元支配梨状皮质和嗅结节。这些新的发现表明，腺苷通过A2AR抑制啮齿类动物的REM睡眠。
Rapid eye movement (REM) sleep behavior disorder in humans is often accompanied by a reduced ability to smell and detect odors, and olfactory bulbectomized rats exhibit increased REM sleep, suggesting that the olfactory bulb (OB) is involved in REM-sleep regulation. However, the molecular mechanism of REM-sleep regulation by the OB is unknown. Adenosine promotes sleep and its A2Areceptors (A2AR) are expressed in the OB. We hypothesized that A2AR in the OB regulate REM sleep. Bilateral microinjections of the A2AR antagonist SCH58261 into the rat OB increased REM sleep, whereas microinjections of the A2AR agonist CGS21680 decreased REM sleep. Similar to the A2AR antagonist, selective A2AR knockdown by adeno-associated virus carrying short-hairpin RNA for A2AR in the rat OB increased REM sleep. Using chemogenetics on the basis of designer receptors exclusively activated by designer drugs, we demonstrated that the inhibition of A2AR neurons increased REM sleep, whereas the activation of these neurons decreased REM sleep. Moreover, using a conditional anterograde axonal tract-tracing approach, we found that OB A2AR neurons innervate the piriform cortex and olfactory tubercle. These novel findings indicate that adenosine suppresses REM sleep via A2AR in the OB of rodents.