受賞記念講演
Neuroscience Research (NSR) 論文賞 Best Paper Award
座長：大塚 稔久（山梨大学） |
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| 2022年7月1日 14:30～15:30 沖縄コンベンションセンター 劇場棟 第1会場
2AL-01a
２つの高睡眠圧マウスモデル間の脳メタボロームの交差比較と、共通変動した代謝物の薬理学的効果の検討
Metabolomic and pharmacologic analyses of brain substances associated with sleep pressure in mice
*鈴木 遥(1,2)
1. 筑波大学 国際統合睡眠医科学研究機構、2. 筑波大学 プレシジョンメディスン開発研究センター
*Haruka Suzuki-Abe(1,2)
1. International Institute for Integrative Sleep Medicine, University of Tsukuba, 2. Research and Development Center for Precision Medicine, University of Tsukuba
Keyword: Sleep pressure, metabolomics, imidazole dipeptides, Sik3
Sleep pressure, the driving force of the homeostatic sleep regulation, is accumulated during wakefulness and dissipated during sleep. Sleep deprivation (SD) has been used as a method to acutely increase animal's sleep pressure for investigating the molecular changes under high sleep pressure. However, SD induces changes not only reflecting increased sleep pressure but also inevitable stresses and prolonged wake state itself. The Sik3Sleepy mutant mice (Sleepy) exhibit constitutively high sleep pressure despite sleeping longer, and have been useful as a model of increased sleep pressure. Here we conducted a cross-comparison of brain metabolomic profiles between SD versus ad lib slept mice, as well as Sleepy mutant versus littermate wild-type mice. Targeted metabolome analyses of whole brains quantified 203 metabolites in total, of which 43 metabolites showed significant changes in SD, whereas three did in Sleepy mutant mice. The large difference in the number of differential metabolites highlighted limitations of SD as methodology. The cross-comparison revealed that a decrease in betaine and an increase in imidazole dipeptides are associated with high sleep pressure in both models. These metabolites may be novel markers of sleep pressure at the whole-brain level. Furthermore, we found that intracerebroventricular injection of imidazole dipeptides increased subsequent NREM sleep time, suggesting the possibility that imidazole dipeptides may participate in the regulation of sleep in mice. | | | |
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