title: PKC in rat dorsal raphe nucleus plays a key role in sleep-wake regulation.
abstract: Studies suggest a tight relationship between protein kinase C (PKC) and circadian clock. However, the role of PKC in sleep-wake regulation remains unclear. The present study was conducted to investigate the role of PKC signaling in sleep-wake regulation in the rat. Our results showed that the phosphorylation level of PKC in dorsal raphe nucleus (DRN) was decreased after 6h sleep deprivation, while no alterations were found in ventrolateral preoptic nucleus (VLPO) or locus coeruleus (LC). Microinjection of a pan-PKC inhibitor, chelerythrine chloride (CHEL, 5 or 10nmol), into DRN of freely moving rats promoted non rapid eye movement sleep (NREMS) without influences on rapid eye movement sleep (REMS). Especially, CHEL application at 5nmol increased light sleep (LS) time while CHEL application at 10nmol increased slow wave sleep (SWS) time and percentage. On the other hand, microinjection of CaCl2 into DRN not only increased the phosphorylation level of PKC, but also reduced NREMS time, especially SWS time and percentage. While CHEL abolished the inhibitory effect of CaCl2 on NREMS and SWS. These data provide the first direct evidence that inhibition of intracellular PKC signaling in DRN could increase NREMS time including SWS time and percentage, while activation of PKC could suppress NREMS and reduce SWS time and percentage. These novel findings further our understanding of the basic cellular and molecular mechanisms of sleep-wake regulation.
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Sheng-Jie
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Xue-Qiong
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Zhao-Fu
authors.initials: ZF
authors.lastname: Sheng
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Zhi-Ge
authors.initials: ZG
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China. Electronic address: zhyh@hsc.pku.edu.cn.
authors.forename: Yong-He
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D017610:Calcium Compounds / Q000494:pharmacology; D002704:Chlorates / Q000494:pharmacology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D008845:Microinjections; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012892:Sleep Deprivation; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D053119:Benzophenanthridines; D017610:Calcium Compounds; D002704:Chlorates; D004791:Enzyme Inhibitors; C091366:calcium chlorate; C016299:chelerythrine; D011493:Protein Kinase C
keywords: Dorsal raphe nucleus; Protein kinase C; Serotonin; Sleep; Slow wave sleep