The role of lipid metabolism in brain functions and sleep

• Project/Area Number: 23730706
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental psychology
• Research Institution: The University of Tokushima
• Principal Investigator: CHIKAHISA Sachiko 徳島大学, ヘルスバイオサイエンス研究部, 助教 (00452649)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 脂質代謝 / 睡眠 / 高次脳機能 / ケトン体 / PPARα

Research Abstract

We investigated the role of brain lipid metabolism in higher brain functions including sleep regulations. Six-hour sleep deprivation markedly increased plasma ketone body concentration in mice. Moreover, sleep deprivation activated ketogenesis in the brain. We also found that icv injection of ketone bodies enhanced sleep depth and decreased glutamate release in freely moving mice. In the brain, astrocyte is known to produce ketone bodies from fatty acids. Lipid metabolism in the astrocyte may play a significant role in brain functions including sleep homeostasis.

Research Products

• [Journal Article] Ketone body metabolism and sleep homeostasis in mice (2014)
  • Author(s): Chikahisa S, Shimizu N, Shiuchi T, Sei H
  • Journal Title: Neuropharmacology Volume: 79 Pages: 399-404
  • DOI: 10.1016/j.neuropharm.2013.12.009
  • Peer Reviewed / Open Access
• [Journal Article] Ketone body metabolism and sleep homeostasis in mice. (2014)
  • Author(s): Chikahisa S, Shimizu N, Shiuchi T, Sei H.
  • Journal Title: Neuropharmacology Volume: 79 Pages: 399-404
  • Peer Reviewed
• [Journal Article] Histamine from brain resident mast cells promotes wakefulness and modulates behavioral states. (2014)
  • Author(s): Chikahisa S, Kodama T, Soya A, Sagawa Y, Ishimaru Y, Sei H, Nishino S.
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] Histamine from brain resident mast cells promotes wakefulness and modulates behavioral states (2013)
  • Author(s): Chikahisa S, Kodama T, Soya A, Sagawa Y, Ishimaru Y, Sei H, Nishino S
  • Journal Title: PLoS One Volume: 8 Issue: 10 Pages: e78434-e78434
  • DOI: 10.1371/journal.pone.0078434
  • Peer Reviewed
• [Journal Article] Maternal dietary restrictionalters offspring's sleep homeostasis (2013)
  • Author(s): Shimizu N, Chikahisa S, Nishi Y, Harada S, Iwaki Y, Shiuchi T, Fujihara H, Kitaoka K, Sei H
  • Journal Title: Plos One Volume: in press Issue: 5 Pages: e64263-e64263
  • DOI: 10.1371/journal.pone.0064263
  • Peer Reviewed
• [Journal Article] The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice (2013)
  • Author(s): Kazuyoshi Kitaoka, Noriyuki Shimizu, Koji Ono, Sachiko Chikahisa, Madoka Nakagomi, Koichi Shudo, Kazunori Ishimura, Hiroyoshi Sei, Kazuo Yoshizaki
  • Journal Title: Neuropharmacology Volume: 72 Pages: 58-65
  • DOI: 10.1016/j.neuropharm.2013.04.009
  • Peer Reviewed
• [Journal Article] Maternal dietary restriction alters offspring's sleep homeostasis. (2013)
  • Author(s): Shimizu N, Chikahisa S, Nishi Y, Harada S, Iwaki Y, Fujihara H, Kitaoka K, Shiuchi Sei H.
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice. (2013)
  • Author(s): Kitaoka K, Shimizu N, Ono K, Chikahisa S, Nakagomi M, Shudo K, Ishimura K, Sei H, Yoshizaki K.
  • Journal Title: Neuropharmacology Volume: 72 Pages: 58-65
  • Peer Reviewed
• [Journal Article] Maternal dietary restriction alters offspring's sleep homeostasis, (2013)
  • Author(s): Shimizu N et al.
  • Journal Title: PlosOne Volume: in Press
• [Journal Article] Sleep regulatory mechanisms (2012)
  • Author(s): Sei H et al.
  • Journal Title: Nihon Rinsho Volume: 70 Pages: 1133-1138
• [Journal Article] The role of ATP in sleep regulation. (2011)
  • Author(s): Chikahisa S, Sei H
  • Journal Title: Front Neurol Volume: 2 Pages: 87-87
  • DOI: 10.3389/fneur.2011.00087
  • Peer Reviewed
• [Journal Article] Refeeding after a 24-hour fasting deepens NREM sleep in a time-dependent manner (2011)
  • Author(s): Shimizu N, Chikahisa S, Kitaoka K, Nishino S, Sei H
  • Journal Title: Physiol Behav Volume: 104(3) Issue: 3 Pages: 480-487
  • DOI: 10.1016/j.physbeh.2011.05.011
  • Peer Reviewed
• [Journal Article] Retinoic acid receptor antagonist LE540 attenuates wakefulness via the dopamine D1 receptor in mice (2011)
  • Author(s): Kitaoka K, Shimizu M, Shimizu N, Chikahisa S, Yoshizaki K, Nakagomi M, Shudo Koichi, Sei H
  • Journal Title: Brain Research Volume: 1423 Pages: 10-16
  • DOI: 10.1016/j.brainres.2011.09.023
  • Peer Reviewed
• [Journal Article] Using iPSC-derived neurons to uncover phenotype (2011)
  • Author(s): Pasca SP et al.
  • Journal Title: Nature Medicine Volume: 17 Pages: 1657-1662
  • Peer Reviewed
• [Journal Article] Refeeding after fasting deepens NREM sleep (2011)
  • Author(s): Shimizu N et al.
  • Journal Title: Physiology & Behavior Volume: 104 Pages: 480-487
  • Peer Reviewed
• [Journal Article] LE540 antagonist attenuates wakefulness (2011)
  • Author(s): Kitaoka K et al.
  • Journal Title: Brain Res Volume: 1423 Pages: 10-16
  • Peer Reviewed
• [Presentation] Ketone bodies in the brain regulate sleep homeostasis in mice (2014)
  • Author(s): Chikahisa S, Shimizu N, Shiuchi T, Shiuchi T, Sei H
  • Organizer: Gordon Research Conference on Sleep Regulation and Function
  • Place of Presentation: Hotel Galveston, USA
• [Presentation] Ketone bodies in the brain regulate sleep homeostasis in mice (2014)
  • Author(s): Chikahisa S, Shimizu N, Shiuchi T, Shiuchi T, Sei H
  • Organizer: Gordon Research Conference on Sleep Regulation and Function
  • Place of Presentation: Hotel Galveston (USA)
• [Presentation] Ketone bodies regulate sleep homeostasis (2013)
  • Author(s): Chikahisa S, Shimizu N, Shiuchi T, Shiuchi T, Sei H
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego Convention Center, USA
• [Presentation] 中枢脂質代謝と睡眠 (2013)
  • Author(s): 近久幸子,勢井宏義
  • Organizer: 日本睡眠学会第38回定期学術集会(シンポジウム)
  • Place of Presentation: 秋田キャッスルホテル(秋田県・秋田市)
• [Presentation] 脳内ケトン体代謝が睡眠ホメオスタシスへ及ぼす影響 (2013)
  • Author(s): 近久幸子,清水紀之,志内哲也,藤原広明,勢井宏義
  • Organizer: 日本睡眠学会第38回定期学術集会
  • Place of Presentation: 秋田キャッスルホテル(秋田県・秋田市)
• [Presentation] Ketone bodies regulate sleep homeostasis (2013)
  • Author(s): Chikahisa S, Shimizu N, Shiuchi T, Shiuchi T, Sei H
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego Convention Center (USA)
• [Presentation] 中枢脂質代謝と睡眠 (2013)
  • Author(s): 近久幸子，勢井宏義
  • Organizer: 日本睡眠学会第38回定期学術集会
  • Place of Presentation: 秋田キャッスルホテル (秋田県)
• [Presentation] Effects of icv administration of a mast cell histamine release enhancer on sleep/wake in wild-type and mast cell deficient mice (2012)
  • Author(s): Chikahisa S, Kodama T, Sagawa Y, Ishimaru Y, Sei H, Nishino S
  • Organizer: Sleep 2012 : 26th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Hynes Veterans Memorial Convention Center Boston, USA
• [Presentation] 脳内脂質代謝と睡眠 (2012)
  • Author(s): 近久幸子,勢井宏義
  • Organizer: 日本睡眠学会第37回定期学術集会(シンポジウム)
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市)
  • Invited
• [Presentation] Sleep homeostatic regulations in PPARα-knockout mice (2012)
  • Author(s): Chikahisa S, Shimizu N, Fujihara H, Shiuchi T, Sei H
  • Organizer: Frontiers in Behavioral Brain Science-Solving the mystery of sleep-
  • Place of Presentation: Tokyo International Forum Hall, Japan
• [Presentation] Effects of icv administration of a mast cell histamine release enhancer on sleep/wake in wild-type and mast cell deficient mice (2012)
  • Author(s): Chikahisa S et al.
  • Organizer: 26th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Hynes Veterans Memorial Convention Center (USA)
• [Presentation] 脳内脂質代謝と睡眠 (2012)
  • Author(s): 近久幸子，勢井宏義
  • Organizer: 日本睡眠学会第37回定期学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Invited
• [Presentation] Sleep homeostatic regulations in PPARα-KO mice (2012)
  • Author(s): Chikahisa S et al.
  • Organizer: Frontiers in Behavioral Brain Science
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] PPARs, AMPK and sleep homeostasis (2011)
  • Author(s): Chikahisa S, Sei H
  • Organizer: 36th Japanase Society of Sleep Research-World sleep 2011 (シンポジウム)
  • Place of Presentation: Kyoto International Conference Center, Japan
• [Presentation] Sleep/wake regulation in PPARα knockout mice (2011)
  • Author(s): Chikahisa S, Shimizu N, Kitaoka K, Iwaki Y, Fujihara H, Shiuchi T, Sei H
  • Organizer: Japanase Society of Sleep Research-World sleep 2011
  • Place of Presentation: Kyoto International Conference Center, Japan
• [Presentation] AMPK and PPARα contribute to sleep homeostasis (2011)
  • Author(s): Chikahisa S
  • Organizer: Sleep 2011 : 25th Anniversary Meeting of the Associated Professional Sleep Societies (シンポジウム)
  • Place of Presentation: Minneapolis Convention Center, USA
• [Presentation] Brain resident mast cells affect sleep/wake physiology and pharmacology (2011)
  • Author(s): Chikahisa S, Sagawa Y, Ishimaru Y, Sakai N, Okuro M, Nishino S
  • Organizer: Sleep 2011 : 25th Anniversary Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Minneapolis Convention Center, USA
• [Presentation] 中枢のPPARαは睡眠制御に寄与する (2011)
  • Author(s): 近久幸子,清水紀之,北岡和義,勢井宏義
  • Organizer: 第88回日本生理学会
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市)
• [Presentation] PPARs, AMPK and sleep homeostasis (2011)
  • Author(s): Chikahisa S
  • Organizer: 36th Japanase Society of Sleep Research(招待講演)
  • Place of Presentation: 国立京都国際会館（京都市）
• [Presentation] AMPK and PPARα contribute to sleep homeostasis (2011)
  • Author(s): Chikahisa S
  • Organizer: 25th APSS(招待講演)
  • Place of Presentation: ミネアポリスコンベンションセンター（USA)
• [Presentation] Sleep/wake regulation in PPARα knockout mice (2011)
  • Author(s): Chikahisa S et al.
  • Organizer: World sleep 2011
  • Place of Presentation: 国立京都国際会館（京都市）
• [Presentation] Brain mast cells affect sleep/wake physiology (2011)
  • Author(s): Chikahisa S et al.
  • Organizer: 25th APSS
  • Place of Presentation: ミネアポリスコンベンションセンター（USA)
• [Book] 睡眠障害 知る診る治す,2章睡眠のメカニズム,3章 ノンレム・レム期の脳の働き,4章 睡眠リズムの変化のメカニズム (2014)
  • Author(s): 近久幸子
  • Total Pages: 216
  • Publisher: メジカルビュー社
• [Book] 睡眠障害 知る診る治す (2014)
  • Author(s): 近久幸子（分担：2章、3章、4章）
  • Total Pages: 216
  • Publisher: メジカルビュー社
• [Book] 脳とこころのプライマリ・ケア,第5巻 意識と睡眠,3章 神経伝達物質と睡眠 (2012)
  • Author(s): 近久幸子,西野精治
  • Total Pages: 840
  • Publisher: 株式会社シナジー出版
• [Book] 脳とこころのプライマリ・ケア，第5巻 意識と睡眠，3章 神経伝達物質と睡眠 (2012)
  • Author(s): 近久幸子，西野精治
  • Publisher: 株式会社シナジー出版