| Project/Area Number |
22K17828
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 59040:Nutrition science and health science-related
|
|---|
| Research Institution | Kagawa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2022-04-01 – 2024-03-31
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
|---|
| Keywords | SAMP8 mouse / neurodegeneration / aging / brainstem / microRNA / neurogeneration / micro RNA / SAMR1 mice / SAMP8 mice |
|---|
| Outline of Research at the Start |
1. 20週齢のSAMR1とSAMP8の認知機能評価と組織学的な差を確認する．
2. 海馬，嗅球，大脳皮質，脳梁，脳幹等の解剖学的に異なる部位別にエクソソーム中のmiRNAを測定し，特異的に発現が亢進または低下するmiRNAを同定する．
3. その結果を用いてSAMR1群とSAMP8群の群間差から得られるmiRNAの差と，それぞれの群内における解剖学的に異なる部位別のmiRNAの発現差が有意なものを同定する．その中で，老化性変化の拡がりのmodulatorとなる可能性のあるものを抽出する．
4. 変性のmodulatorと考え得る蛋白を同定し，神経変性を抑制するターゲットになり得るか検討する．
|
| Outline of Final Research Achievements |
In the present study, microRNAs (miRNAs) that were upregulated or downregulated in SAMP8 brainstems were identified using miRNA profiling of samples obtained from miRNA arrays. The preliminary stage of cognitive dysfunction was examined using male 5-month-old SAMP8 mice, with age-matched senescence-accelerated mouse resistant 1 (SAMR1) mice as controls. A Y-maze alternation test was performed to assess short-term working memory, and miRNA profiling was conducted in each region of the dissected brain. SAMP8 mice tended to be hyperactive, but short-term working memory was preserved. Two miRNAs were upregulated (miR-491-5p and miR-764-5p), and two were downregulated (miR-30e-3p and miR-323-3p) in SAMP8 brainstems. Changes in miRNA expression may lead to the induction of target proteins during the early stages of neurodegeneration in the brainstem. These findings suggest that studying altered miRNA expression may provide molecular evidence for early age-related neuropathological changes.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究ではモデルマウスを用いることで、早期の段階で変性が生じた部位とその後に変性が拡がることが知られている部位同士を比較することで、miRNAの発現の違いを比較した。老化変性の拡大のトリガーとなるmiRNAやその一連の発現パターンから老化の進行へのヒントを得ることができた。これまではヒトではBraak仮説など、病理学的な老化性変化の拡大パターンは報告されていた。それになぞらうようにモデルマウスでmiRNAの発現パターンを今回の研究では示すことができた。miRNAでは単独の信号変化を追うのではなく、一連の信号変化を考慮した考察が今後は必要であることが予想された。
|
