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

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K07444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Animal physiology/Animal behavior
• Research Institution: Juntendo 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
• Keywords: ショウジョウバエ / 概日リズム / 老化 / 遺伝子発現

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.

Free Research Field

時間生物学

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。