Ying Zhang, Jiaxin Li, Yan Li, Wei Wang, Daming Wang, Junli Ding, Licheng Wang, Juan Cheng
{"title":"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","authors":"Ying Zhang, Jiaxin Li, Yan Li, Wei Wang, Daming Wang, Junli Ding, Licheng Wang, Juan Cheng","doi":"10.1007/s11064-024-04221-w","DOIUrl":null,"url":null,"abstract":"<div><p>Dexmedetomidine (DEX) is a highly selective α<sub>2</sub>-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVN<sup>OXT</sup>) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVN<sup>OXT</sup> 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<sup>OXT</sup> 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<sup>OXT</sup> 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<sup>OXT</sup> neurons through α<sub>2</sub>-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVN<sup>OXT</sup> neurons through the α<sub>2</sub>-adrenoceptor.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dexmedetomidine Promotes NREM Sleep by Depressing Oxytocin Neurons in the Paraventricular Nucleus in Mice\",\"authors\":\"Ying Zhang, Jiaxin Li, Yan Li, Wei Wang, Daming Wang, Junli Ding, Licheng Wang, Juan Cheng\",\"doi\":\"10.1007/s11064-024-04221-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Dexmedetomidine (DEX) is a highly selective α<sub>2</sub>-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVN<sup>OXT</sup>) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVN<sup>OXT</sup> 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<sup>OXT</sup> 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<sup>OXT</sup> 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<sup>OXT</sup> neurons through α<sub>2</sub>-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVN<sup>OXT</sup> neurons through the α<sub>2</sub>-adrenoceptor.</p></div>\",\"PeriodicalId\":719,\"journal\":{\"name\":\"Neurochemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurochemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11064-024-04221-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11064-024-04221-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.