Underlying mechanisms for induction of hypothermia in homeothermic animals

• Project/Area Number: 16K15189
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Gunma University
• Principal Investigator: Sato-Hashimoto Miho 群馬大学, 大学院保健学研究科, 研究員 (90381087)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: SIRPα / 全身性炎症反応症候群 / 低体温 / LPS / hypothermia / 脳 / 体温調節 / 低体温誘導機構

Outline of Final Research Achievements

SIRPα KO mice show high sensitivities against LPS treatments, resulted in hypothermia with low doses. In this study, therefore, we focused on the mechanisms underlying LPS-induced hypothermia. After treatments of LPS, the metabolism underwent lower actively in SIRPα KO mice, that is probably caused by strong inflammatory responses in the brain. In addition, hypothermia and immune reflex mediating the vagus nerve might inhibit inflammation in the peripheral organs. Hypothermia found in the systematic inflammatory response is the active response to suppress the excessive inflammation, but it might not be caused by the failure of thermoregulation.

Academic Significance and Societal Importance of the Research Achievements

LPS投与に誘導される低体温は、代謝抑制が原因であることが明らかになったことは本研究の成果である。またSIRPα KOマウスは、脳内のミクログリアが恒常的に活性化した状態にあり、このことが強い低体温の誘導に関わる可能性がある。ミクログリアの活性化は、老齢の動物の脳で見られる特徴と同様であることから、本研究は高齢者に全身性炎症反応が起こった際の体温調節機構を理解する上で重要な知見となるであろう。

Research Products

• [Journal Article] Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter. (2019)
  • Author(s): Sato-Hashimoto M, Nozu T, Toriba R, Horikoshi A, Akaike M, Kawamoto K, Hirose A, Hayashi H, Nagai H, Shimizu W, Saiki A., Ishikawa T, Elhanbaly R, Kotani T, Murata Y, Saito Y, Naruse M, Shibasaki K, Oldenborg P.-A, Jung S, Matozaki T, Fukazawa Y, Ohnishi H.
  • Journal Title: eLife Volume: - Pages: 1-29
  • DOI: 10.7554/elife.42025
  • NAID: 120006604638
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Induction of long-term torpor by enhancing the adenosine receptor signal via PPARs. (2019)
  • Author(s): Miho Sato-Hashimoto, Hiroshi Ohnishi
  • Organizer: 9th FAOPS congress・第96回日本生理学会大会
• [Presentation] Study of stress-induced tyrosine phosphorylation of SIRPα in immortalized murine microglia cell line. (2018)
  • Author(s): Daiki Jingu, Ayaka Motai, Mika Iino, Joji Kawasaki, Kaori Imai, Miho Sato-Hashimoto, Hiroshi Ohnishi
  • Organizer: Workshop on Frontiers in Phosphatase Research and Drug Discovery
• [Presentation] Analysis of stress-induced tyrosine phosphorylation of SIRPα in primary cultured neurons. (2018)
  • Author(s): Mika Iino, Joji Kawasaki, Daiki Jingu, Ayaka Motai, Kaori Imai, Miho Sato-Hashimoto, Hiroshi Ohnishi
  • Organizer: Workshop on Frontiers in Phosphatase Research and Drug Discovery
• [Presentation] Control of microglia activation by SIRPα. (2018)
  • Author(s): Hiromi Nagai, Ayuto Shimoda, Tomomi Nozu, Ayano Horikoshi, Miho Akaike, Yuriko Hayashi, Miho Sato-Hashimoto, Hiroshi Ohnishi
  • Organizer: Workshop on Frontiers in Phosphatase Research and Drug Discovery
• [Presentation] A molecular signal that controls tissue damage and repair in the brain white matter. (2018)
  • Author(s): Hiromi Nagai, Miho Hashimoto, Ayano Horikoshi, Ruwaida Elhanbaly, Tatsuya Ishikawa, Takashi Matozaki, Yugo Fukasawa, Hiroshi Ohnishi
  • Organizer: 第40回日本生物学的精神医学会・第61回日本神経化学会大会
• [Presentation] Study of stress-induced tyrosine phosphorylation of SIRPα in immortalized murine microglia cell line. (2018)
  • Author(s): Daiki Jingu, Ayaka Motai, Mika Iino, Joji Kawasaki, Kaori Imai, Miho Sato-Hashimoto, Takashi Matozaki, Hiroshi Ohnishi
  • Organizer: 第40回日本生物学的精神医学会・第61回日本神経化学会大会
• [Presentation] PPARsの活性化がアデノシンA1受容体作動薬による低体温を長期化する (2018)
  • Author(s): 橋本美穂, 大西浩史
  • Organizer: 第17回生体機能研究会
• [Presentation] ペルオキシゾーム増殖剤活性化受容体の活性化はアデノシンA1受容体作動薬によって誘導される低体温を長期化する (2018)
  • Author(s): 橋本美穂, 大西浩史
  • Organizer: 第41回日本神経科学大会
• [Presentation] マウスの低体温症から低体温誘導メカニズムを考える (2017)
  • Author(s): 橋本美穂
  • Organizer: 第１回冬眠休眠研究会
• [Presentation] SIRPαシグナルの欠損がミクログリアに与える影響 (2017)
  • Author(s): 橋本美穂、堀越絢乃、永井裕美、神宮大輝、赤池美穂、浦野江里子、的崎尚、大西浩史
  • Organizer: 第１６回生体機能研究会
• [Presentation] The effect of genetic ablation of CD47-SIRPα signal on microglial activation and pathology of demyelination. (2017)
  • Author(s): Ayano Horikoshi, Miho Hashimoto, Hiromi Nagai, Hiroshi Ohnishi
  • Organizer: 第８回日本プロテインホスファターゼ研究会学術集会
• [Presentation] The impact of ion dynamics on tyrosine phosphorylation of SIRPα. (2017)
  • Author(s): Daiki Jingu, Mika Iino, Shinya Kusakari, Miho Hashimoto, Hiroshi Ohnishi
  • Organizer: 第８回日本プロテインホスファターゼ研究会学術集会
• [Presentation] Possible roles of thyroid hormones in hibernation control. (2016)
  • Author(s): Miho Sato-Hashimoto, Tsuneo Sekijima, Takashi Ohtsu, Taito Kamata, Hiroshi Ohnishi, Noriaki Kondo
  • Organizer: 第87回日本動物学会
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2016-11-17
• [Presentation] Systemic regulation of circannual changes in hibernation-specific protein by thyroid hormone metabolism. (2016)
  • Author(s): Miho Sato-Hashimoto, Tsuneo Sekijima, Takashi Ohtsu, Noriaki Kondo
  • Organizer: The 22nd International Congress of Zoology
  • Place of Presentation: 沖縄科学技術大学院大学
  • Year and Date: 2016-11-14
  • Int'l Joint Research / Invited
• [Presentation] Analysis of a direct cell-cell communication signal that regulates glial acrivation in the brain. (2016)
  • Author(s): Tomomi Nozu, Miho Hashimoto, Ruwaida Elhanbaly, Tatsuya Ishikawa, Ayaka Hirose, Waka Shimizu, Takashi Matozaki, Yugo Fukazawa, Hiroshi Ohnishi
  • Organizer: 第12回プロテインホスファターゼ国際カンファレンス
  • Place of Presentation: 近畿大学
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] SIRPα欠損マウスにおけるクプリゾン感受性の亢進 (2016)
  • Author(s): 野津智美、橋本美穂,Ruwaida Elhanbaly, 石川達也、齊藤泰之、小谷武徳、村田陽二、深澤有吾、的崎尚、大西浩史
  • Organizer: 第63回北関東医学会総会
  • Place of Presentation: 群馬大学刀城会館
  • Year and Date: 2016-09-29
• [Presentation] SIRPα欠損マウスはLPS投与によって誘導される低体温症が重症化する (2016)
  • Author(s): 橋本美穂、野津智美、浦野江里子、齊藤泰之、小谷武徳、村田陽二、的崎尚、大西浩史
  • Organizer: 第38回日本生物学的精神医学会・第59回日本神経化学会大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-09-08
• [Presentation] 白質におけるミクログリア恒常性制御 (2016)
  • Author(s): 野津智美、橋本美穂、Ruwaida Elhanbaly、 石川達也、齊藤泰之、小谷武徳、村田陽二、的崎尚、深澤有吾、大西浩史
  • Organizer: 第38回日本生物学的精神医学会・第59回日本神経化学会大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-09-08