右美托咪定通过抑制小鼠脑室旁核中的催产素神经元促进 NREM 睡眠

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemical Research Pub Date : 2024-07-30 DOI:10.1007/s11064-024-04221-w
Ying Zhang, Jiaxin Li, Yan Li, Wei Wang, Daming Wang, Junli Ding, Licheng Wang, Juan Cheng
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引用次数: 0

摘要

右美托咪定(DEX)是一种高选择性α2肾上腺素受体激动剂,对睡眠平衡具有镇静作用。下丘脑室旁核(PVN)中表达催产素(OXT)的神经元(PVNOXT)调节性繁殖、饮酒、睡眠觉醒和其他本能行为。为了研究DEX对PVNOXT调节睡眠-觉醒周期的活性和信号传递的影响。在这里,我们利用OXT-cre小鼠在PVNOXT神经元中选择性地靶向和表达基于DREADD的化学遗传工具hM3D(Gq)。结合化学遗传学方法和脑电图(EEG)/肌电图(EMG)记录,我们发现在PVN中插管注射DEX能显著延长小鼠非快速眼动(NREM)睡眠的持续时间。此外,在PVN插管注射DEX后,使用氯氮平N-氧化物(CNO)对PVNOXT神经元进行化学激活,可使小鼠的觉醒时间大幅增加。电生理结果显示,DEX通过α2-肾上腺素受体降低了PVNOXT神经元的动作电位(AP)频率和突触后自发兴奋电流(sEPSC)。因此,这些结果表明,DEX通过α2-肾上腺素受体抑制PVNOXT神经元,从而促进睡眠和维持睡眠平衡。
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Dexmedetomidine Promotes NREM Sleep by Depressing Oxytocin Neurons in the Paraventricular Nucleus in Mice

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVNOXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVNOXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVNOXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVNOXT neurons through α2-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVNOXT neurons through the α2-adrenoceptor.

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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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