2021 Fiscal Year Annual Research Report
Elucidation of sleep/wakefulness regulation using forward genetic approach
Project/Area Number |
17H06095
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Research Institution | University of Tsukuba |
Principal Investigator |
柳沢 正史 筑波大学, 国際統合睡眠医科学研究機構, 教授 (20202369)
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Co-Investigator(Kenkyū-buntansha) |
船戸 弘正 筑波大学, 国際統合睡眠医科学研究機構, 客員教授 (90363118)
Liu Qinghua 筑波大学, 国際統合睡眠医科学研究機構, 教授 (90723792)
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Project Period (FY) |
2017-04-25 – 2022-03-31
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Keywords | 睡眠覚醒 / 脳神経 / 遺伝子改変マウス / ゲノム編集 / 細胞内シグナル伝達系 |
Outline of Annual Research Achievements |
睡眠は動物に普遍的に認められる行動であり、その不調は心身の疾患リスクを高める。しかし、睡眠覚醒行動を制御する神経科学的メカニズムは不明である。本研究は、睡眠のフォワード・ジェネティクス研究により新規睡眠制御分子を同定するとともに、リン酸化酵素SIK3およびリークチャネルNALCNによる睡眠覚醒制御機構解明を目指している。前年度に引き続き脳波筋電図にもとづくランダム点突然変異マウスの睡眠異常スクリーニングを行い遺伝性に睡眠異常を示す個体の同定、睡眠表現型の遺伝性の確認、連鎖解析及び全エクソームシーケンスによる責任遺伝子変異の同定を進めた。同定された遺伝子についてはAAV-PHP.eBを用いたり、CRISPR法により遺伝子改変マウスを作成して因果性の確認を行っている。SIK3変異を標的としたサプレッサースクリーニングも進めており、SIK3遺伝子変異が存在してもノンレム睡眠量が正常化する家系を樹立している。SIK3パスウェイを構成する遺伝子を操作したマウスを過眠モデルとして用いてマルチオミクス解析を行っている。メタボローム解析によって睡眠を促進する効果を持つメタボライトを同定した。プロテオーム、トランスクリプトーム解析も並行して実施し、異なる過眠モデル脳で共通した変化を示す分子を同定した。陽イオンリークチャネルNALCNのニューロンタイプ特異的なレム断片化DRL変異誘導や機能欠失によって多彩なレム睡眠異常を呈することが明らかとなった。
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Research Progress Status |
令和3年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
令和3年度が最終年度であるため、記入しない。
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Research Products
(83 results)
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[Journal Article] Morning preference is associated with subjective happiness among Japanese female workers: A moderation analysis by sleep characteristics from the SLEPT study2022
Author(s)
Daisuke Hori, Yo Arai, Emi Morita, Yu Ikeda, Kei Muroi, Mami Ishitsuka, Tomohiko Ikeda, Tsukasa Takahashi, Shotaro Doki, Yuichi Oi, Shinichiro Sasahara, Asuka Ishihara, Sumire Matsumoto, Takashi Kanbayashi, Masashi Yanagisawa, Mokoto Satoh, Ichiyo Matsuzaki
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Journal Title
Chronobiology International
Volume: 39
Pages: 690-703
DOI
Peer Reviewed / Open Access
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[Journal Article] Effect of removal of the 14-hydroxy group on the affinity of the 4,5-epoxymorphinan derivatives for orexin and opioid receptors2022
Author(s)
Koki Katoh, Naoshi Yamamoto, Yukiko Ishikawa, Yoko Irukayama-Tomoebe, Ryuji Tanimura, Tsuyoshi Saitoh, Yasuyuki Nagumo, Noriki Kutsumura, Masashi Yanagisawa, Hiroshi Nagase
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Journal Title
Bioorganic & Medicinal Chemistry Letters
Volume: 59
Pages: 128527
DOI
Peer Reviewed / Open Access
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[Journal Article] Discovery of orexin 2 receptor selective and dual orexin receptor agonists based on the tetralin structure: Switching of receptor selectivity by chirality on the tetralin ring2022
Author(s)
Keita Iio, Tsuyoshi Saitoh, Ryuichiro Ohshita, Tsubasa Hino, Mao Amezawa, Yoshiaki Takayama, Yasuyuki Nagumo, Naoshi Yamamoto, Noriki Kustumura, Yoko Irukayama-Tomobe, Yukiko Ishikawa, Ryuji Tanimura, Masashi Yanagisawa, Hiroshi Nagase
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Journal Title
Bioorganic & Medicinal Chemistry Letters
Volume: 60
Pages: 128555
DOI
Peer Reviewed / Open Access
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[Journal Article] Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors2021
Author(s)
Chia-Jung Tsai, Takeshi Nagata, Chih-Yao Liu, Takaya Suganuma, Takeshi Kanda, Takehiro Miyazaki, Kai Liu, Tsuyoshi Saitoh, Hiroshi Nagase, Michael Lazarus, Kaspar E. Vogt, Masashi Yanagisawa, Yu Hayashi
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Journal Title
Cell Reports
Volume: 36
Pages: 109558
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] レム睡眠制御の分子機構:近位依存性ビオチン標識法BioIDを用いた電位非依存性陽イオンチャネルNALCNのタンパク質間相互作用因子の探索2022
Author(s)
藤山知之, 山元ひかり, 北園智弘, 一久綾, 管野里美, 柿﨑美代, Choi Jinhwan, 中田慎也, 村田知弥, 水野聖哉, 杉山文博, 高橋智, 船戸弘正, 柳沢正史
Organizer
第95回日本薬理学会年会
Int'l Joint Research
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[Presentation] NALCN in the forebrain and pons-medulla regions have distinct roles in REM sleep regulation2022
Author(s)
Tomoyuki Fujiyama, Satomi Kanno, Noriko Hirashima Hotta, Miyo Kakizaki, Aya Ikkyu, Yosuke Tsuneoka, Manabu Abe, Ayako Mochizuki, Patricia Seoane-Collazo, Takehiro Miyazaki, Seiya Mizuno, Chika Miyoshi, Takeshi Kanda, Masahiko Watanabe, Kenji Sakimura, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
第99回日本生理学会JST-CREST "Opt Bio" /WPI-IIIS Joint Symposium
Int'l Joint Research
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[Presentation] Orexin receptor antagonists ameliorate the symptoms of REM sleep behavior disorder in a novel mouse model and in human patients2022
Author(s)
Mari Hondo, Takuro Endo, Ayako Mochizuki, Masanori Dantsuji, Takeshi Kanda, Makito Sato, Fusae Kawana, Yukiko Ishikawa, Kazue Suenaga, Shiro Nakamura, Manabu Abe, Tomio Inoue, Kenji Sakimura, Hiromasa Funato, Takeshi Sakurai, Masashi Yanagisawa
Organizer
第99回日本生理学会JST-CREST "Opt Bio" /WPI-IIIS Joint Symposium
Int'l Joint Research
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[Presentation] Sik3 regulates sleep need via glutamatergic neurons in cerebral cortex2022
Author(s)
Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Tomohiro Kitazono, Noriko Hotta-Hirashima, Miyo Kakizaki, Aya Ikkyu, Satomi Kanno, Shinya Nakata, Nodoka Asama, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
第99回日本生理学会JST-CREST "Opt Bio" /WPI-IIIS Joint Symposium
Int'l Joint Research
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[Presentation] Where does Sleepy mutation of SIK3 cause sleep phenotypes?2022
Author(s)
Kanako Iwasaki, Tomoyuki Fujiyama, Shinya Nakata, Minjeong Park, Chika Miyoshi, Noriko Hotta-Hirashima, Aya Ikkyu, Miyo Kakizaki, Yukiko Ishikawa, Fumihiro Sugiyama, Seiya Mizuno, Manabu Abe, Kenji Sakimura, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
第99回日本生理学会JST-CREST "Opt Bio" /WPI-IIIS Joint Symposium
Int'l Joint Research
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[Presentation] Molecular mechanisms for SIK3(Sleepy)-mediated sleep/wake regulation2022
Author(s)
Shinya Nakata, Haruna Abe-Komiya, Tomoyuki Fujiyama, Chika Miyoshi, Aya Ikkyu, Fuyuki Asano, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
第99回日本生理学会JST-CREST "Opt Bio" /WPI-IIIS Joint Symposium
Int'l Joint Research
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[Presentation] OX2R-selective orexin agonism is sufficient to suppress narcoleptic symptoms, cataplexy and wake fragmentation, without inducing drug-seeking behavior in mouse models2022
Author(s)
Hikari Yamamoto, Yasuyuki Nagumo, Yukiko Ishikawa, Yoko Irukayama-Tomobe, Tsuyoshi Nemoto, Hiromu Tanaka, Genki Takahashi, Akihisa Tokuda, Tsuyoshi Saitoh, Hiroshi Nagase, Hiromasa Funato, Masashi Yanagisawa
Organizer
第99回日本生理学会JST-CREST "Opt Bio" /WPI-IIIS Joint Symposium
Int'l Joint Research
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[Presentation] Sleepy mouse as a model of idiopathic hypersomnia2022
Author(s)
Asmaa Elhosainy Mohamed Mahmoud, Haruka Suzuki-Abe, Mahesh Kaushik, Staci Jakyong Kim, Tsuyoshi Saitoh, Yukiko Ishikawa, Noriko HottaHirashima, Chika Miyoshi, Hiromasa Funato, Masashi Yanagisawa
Organizer
第99回日本生理学会JST-CREST "Opt Bio" /WPI-IIIS Joint Symposium
Int'l Joint Research
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[Presentation] Endogenous SIK3 regulates sleep need through glutamatergic neurons in cerebral cortex2021
Author(s)
浅野冬樹, 藤山智之, 三好千香,北園智弘, 堀田範子, 柿﨑美代, 一久綾, 管野里美, 中田慎也, 浅間のどか, 水野聖哉, 杉山文博, 高橋智, 船戸弘正, 柳沢正史
Organizer
第44回日本神経科学大会・CJK第1回国際会議
Int'l Joint Research
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[Presentation] Neuroanatomical and biochemical analysis of how the Sleepy mutant of SIK3 increases sleep2021
Author(s)
岩崎加奈子, 藤山智之, 上田壮志, 中田慎也, Minjeong Park, 三好千香, 堀田範子, 一久綾, 柿﨑美代, 杉山文博, 水野聖哉, 阿部学, 崎村健司, 高橋智, 松田道行, 船戸弘正, 柳沢正史
Organizer
第44回日本神経科学大会
Int'l Joint Research
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[Presentation] Phosphorylation-deficient Sleepy2 mutant mice exhibited decreased NREM sleep2021
Author(s)
浅間のどか, Staci J. Kim, 藤山智之, 浅野冬樹, 三好千香, 堀田範子, 柿﨑美代, 一久綾, 管野里美, 中田慎也, 水野聖哉, 高橋智, 船戸弘正, 柳沢正史
Organizer
第44回日本神経科学大会・CJK第1回国際会議
Int'l Joint Research
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[Presentation] The functional analysis of SIK3 kinase activity for sleep/wake regulation2021
Author(s)
中田慎也, 小宮春奈, 藤山智之, 三好千香, 一久綾, 浅野冬樹, 水野聖哉, 杉山文博, 高橋智, 船戸弘正, 柳沢正史
Organizer
第44回日本神経科学大会・CJK第1回国際会議
Int'l Joint Research
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[Presentation] Molecular mechanisms for SIK3(Sleepy)-mediated sleep/wake regulation2021
Author(s)
Shinya Nakata, Haruna Abe-Komiya, Tomoyuki Fujiyama, Chika Miyoshi, Aya Ikkyu, Fuyuki Asano, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
Tsukuba Conference 2021(筑波会議2021)
Int'l Joint Research
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[Presentation] Perturbation in Hdac4 signaling leads to dysregulated NREMS2021
Author(s)
Staci J. Kim, Noriko Hotta-Hirashima, Nodoka Asama, Taeko Matsuoka, Tomoyuki Fujiyama, Aya Ikkyu, Miyo Kakizaki, Satomi Kanno, Sseiya Mizuno, Satoru Takahashi, Chika Miyoshi, Hiromasa Funato, Masashi Yanagisawa
Organizer
SFN Neuroscience 2021 50th Annual Meeting participation
Int'l Joint Research
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[Presentation] Where does Sleepy mutation of SIK3 increase non-REM sleep?2021
Author(s)
Kanako Iwasaki, Tomoyuki Fujiyama, Shinya Nakata, Minjeong Park, Chika Miyoshi, Noriko Hotta-Hirashima, Aya Ikkyu, Miyo Kakizaki, Yukiko Ishikawa, Fumihiro Sugiyama, Seiya Mizuno, Manabu Abe, Kenji Sakimura, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
NEUROSCIENCE 2021
Int'l Joint Research
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[Presentation] Sik3 regulates sleep need via glutamatergic neurons in cerebral cortex in mice2021
Author(s)
Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Tomohiro Kitazono, Noriko Hotta-Hirashima, Miyo Kakizaki, Aya Ikkyu, Satomi Kanno, Shinya Nakata, Nodoka Asama, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
NEUROSCIENCE 2021
Int'l Joint Research
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[Presentation] Molecular mechanisms of REM sleep regulation: identifying protein-protein interactions of NALCN channel through BioID technique2021
Author(s)
Hikari Yamamoto, Tomoyuki Fujiyama, Tomohiro Kitazono, Aya Ikkyu, Satomi Kanno, Miyo Kakizaki, Choi Jinhwan, Shinya Nakata, Kazuya Murata, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Hiromasa Funato, Masashi Yanagisawa
Organizer
第44回日本分子生物学会年会
Int'l Joint Research
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