Whether reduction of skeletal muscle function causes deterioration of cognitive function or depression symptoms

• Project/Area Number: 16K13047
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: University of Shizuoka
• Principal Investigator: Miura Shinji 静岡県立大学, 食品栄養科学部, 教授 (10342932)
• Co-Investigator(Kenkyū-buntansha): 守田 昭仁 静岡県立大学, 食品栄養科学部, 助教 (40239653)
• Co-Investigator(Renkei-kenkyūsha): KAMEI YASUTOMI 京都府立大学, 生命環境科学研究科, 教授 (70300829) ; ASAI AKIRA 静岡県立大学, 大学院 薬学研究科, 教授 (60381737) ; UNNO KEIKO 静岡県立大学, 薬学部, 准教授 (10106437) ; YOSHIDA TAKUYA 静岡県立大学, 食品栄養科学部, 助教 (80622448)
• Research Collaborator: SATO TOMOKI 静岡県立大学, 大学院 薬食生命科学総合学府 ; SENOO NANAMI 静岡県立大学, 大学院 薬食生命科学総合学府 ; ISHINO MAYU 静岡県立大学, 大学院 薬食生命科学総合学府
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 加齢 / 老化 / 筋萎縮 / 認知機能 / うつ / ストレス / キヌレニン / キヌレン酸 / 加齢・老化

Outline of Final Research Achievements

Kynurenine is produced peripherally by stress exposure and causes depression symptoms in the brain. It was reported that exercise increases KAT expression in skeletal muscle, promotes degradation of kynurenine in the periphery and suppresses stress induced-depression. Therefore, in this study, we examined the hypothesis that "if the skeletal muscle function declines due to inactivity, the degradation of kynurenine is decreased, kynurenine influx into the brain is accelerated, and depressive symptoms worsen". As a result, even if the expression level of KAT of skeletal muscle was decreased, there was little effect on depressive symptoms. Any change in expression level of KAT was not observed in skeletal muscle of muscle atrophy model mouse (FOXO 1 Tg mouse). Injection of kynurenine into FOXO 1 Tg mouse caused no adverse effect on the expression level of hippocampal depression related genes.

Research Products

• [Presentation] KIS-154, a FOXO1 inhibitor, is one of the candidate compounds to prevent skeletal muscle atrophy. (2017)
  • Author(s): Watanabe, Y., Nakagawa, T., Morita, A., Ogo, N., Asai, A., Kamei, Y., and Miura, S.
  • Organizer: The 22nd Shizuoka Forum on Health and Longevity
  • Int'l Joint Research
• [Presentation] 骨格筋の機能低下がキヌレニン代謝および「うつ」症状に与える影響 (2017)
  • Author(s): 石野真悠、守田昭仁、三浦進司
  • Organizer: 第７２回日本体力医学会大会
• [Presentation] 絶食後の骨格筋におけるリン脂質組成変化とFOXO1の関与 (2017)
  • Author(s): 妹尾奈波、三好規之、守田昭仁、亀井康富、三浦進司
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] Foxo1を標的とした筋萎縮抑制化合物の探索 (2017)
  • Author(s): 渡辺優衣、中川匠、守田昭仁、小郷尚久、浅井章良、亀井康富、三浦進司
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] 骨格筋機能低下によるうつ症状への影響 (2017)
  • Author(s): 石野真悠、三浦進司
  • Organizer: 第５回骨格筋生物学研究会
• [Book] 非栄養素の分子栄養学 (2017)
  • Author(s): 畑澤幸乃、三浦進司、亀井康富
  • Total Pages: 251
  • Publisher: 建帛社
  • ISBN: 9784767961897