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Analysis of neural and molecular mechanism of sleep fragmentation with aging in Drosophila

Research Project

Project/Area Number 16K07444
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Animal physiology/Animal behavior
Research InstitutionJuntendo University

Principal Investigator

Matsumoto Akira  順天堂大学, 医学部, 先任准教授 (40229539)

Co-Investigator(Kenkyū-buntansha) 伊藤 太一  九州大学, 基幹教育院, 助教 (20769765)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsショウジョウバエ / 概日リズム / 老化 / 遺伝子発現 / 睡眠相断片化 / 加齢 / 行動計測 / 歩行活動 / RNAseq / 行動解析 / 短周期リズム / 睡眠
Outline of Final Research Achievements

We obtained a typical sigmoidal survival curve with half-lethal of 12 weeks and a maximum lifespan of 17 weeks in females while males are dead monotonically with aging up to 12 weeks. Then we compared 1-week and 10-week-old males focused on the locomotor activities recorded by 1 second bin. The sleep fragmentation was shown every 45 minutes in the old flies.
We sampled 1 and 10-week-old male brains every 6 hours for 3 days, and performed RNAseq analyses. The bioinformatics analysis suggests that 8 to 10 clusters exist in cyclically expressing genes. Each cluster had a characteristic gene function and, in some cases, a common transcription factor. Based on these results, we identified candidate genes those likely to act as the primary cause of aging affecting cyclic gene expression, although a further analysis are necessary to identify how these genes functions in sleep fragmentation in Drosophila neural network.

Academic Significance and Societal Importance of the Research Achievements

加齢に伴う睡眠相断片化による不眠、それに伴う不眠不安症に対する治療法の確立や創薬はQOLの観点からも重要である。本課題では、基礎科学の立場からその原因解明に取り組んだ。研究期間内には、タイトルに掲げた睡眠相断片化に関わる神経回路網の同定には到らなかったが、原因のひとつと思われる液性因子は同定できた。しかし、昆虫特異的なホルモン関連物質で、直ちに創薬などに繋げる事は出来なかった。一方、脳内の遺伝子発現を若齢と老齢で一日の時系列で網羅的に比較することで、周期的な遺伝子発現に加齢が影響を及ぼす際のターゲット遺伝子候補を複数同定できた。解析の進展によっては創薬への貢献が期待できる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 Other

All Int'l Joint Research (2 results) Presentation (2 results) (of which Invited: 1 results) Book (1 results)

  • [Int'l Joint Research] Northwestern University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] ノースウェスタン大学(米国)

    • Related Report
      2017 Research-status Report
  • [Presentation] Cleaning Drosophila’s clock: Unaddressed and unresolved questions about the fruit fly circadian timekeeper2018

    • Author(s)
      松本顕
    • Organizer
      第25回日本時間生物学会学術大会(長崎)シンポジウム「Epoch-making Discoveries in Chronobiology」
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ショウジョウバエ歩行活動に対する加齢の影響2017

    • Author(s)
      松本顕、伊藤太一
    • Organizer
      第24回(2017年度)日本時間生物学会学術大会
    • Related Report
      2017 Research-status Report
  • [Book] 時をあやつる遺伝子2018

    • Author(s)
      松本顕
    • Total Pages
      131
    • Publisher
      岩波書店
    • ISBN
      9784000296755
    • Related Report
      2018 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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