Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China.
Department of Pharmacy, Linquan People's Hospital, Linquan, 236400, Anhui, China.
Neurochem Res. 2024 Oct;49(10):2926-2939. doi: 10.1007/s11064-024-04221-w. Epub 2024 Jul 30.
Dexmedetomidine (DEX) is a highly selective α-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVN) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVN 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 PVN 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 PVN 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 PVN neurons through α-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVN neurons through the α-adrenoceptor.
右美托咪定（DEX）是一种高度选择性的α-肾上腺素受体激动剂，对睡眠稳态具有镇静作用。下丘脑室旁核（PVN）中的催产素表达（OXT）神经元调节生殖、饮水、睡眠-觉醒和其他本能行为。为了研究 DEX 对调节睡眠-觉醒周期的 PVN 活性和信号转导的影响。在这里，我们使用 OXT-cre 小鼠在 PVN 神经元中选择性地靶向和表达基于设计受体的唯一激活剂（DREADD）的化学遗传工具 hM3D(Gq)。结合化学遗传方法和脑电图（EEG）/肌电图（EMG）记录，我们发现 PVN 中的 DEX 套管注射显著增加了小鼠的非快速眼动（NREM）睡眠时间。此外，在 DEX 套管注射后通过腹腔注射氯氮平 N-氧化物（CNO）对 PVN 神经元进行化学遗传激活，导致觉醒显著增加。电生理结果表明，DEX 通过α-肾上腺素受体降低 PVN 神经元动作电位（AP）和自发性兴奋性突触后电流（sEPSC）的频率。因此，这些结果表明，DEX 通过α-肾上腺素受体抑制 PVN 神经元来促进睡眠和维持睡眠稳态。
