2022 Fiscal Year Final Research Report
Cross-talk analysis between heterotypic cell-cell communication via siRNA/TLR7 and new therapeutic strategy
| Project/Area Number |
19K09899
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56050:Otorhinolaryngology-related
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
HAYASHI Ken 慶應義塾大学, 医学部(信濃町), 共同研究員 (80534528)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
神崎 晶 慶應義塾大学, 医学部(信濃町), 講師 (50286556)
高橋 宏知 東京大学, 大学院情報理工学系研究科, 教授 (90361518)
|
|---|
| Project Period (FY) |
2019-04-01 – 2023-03-31
|
| Keywords | エクソソームmiRNA let-7b / 異種細胞間コミュニケーション / ミスマッチネガティビティ / 間歇的自発バースト / 初代神経培養細胞 |
|---|
| Outline of Final Research Achievements |
Our objective is to clarify the impact of exosomal (exo-) miRNA let-7b inducing hyper excitability-induced auditory cell death to the mismatch negativity (MMN) reflecting an auditory memory traces in neural cells. Primary neuronal cells are prepared from Wister rat brains. The stimulation selectivity of the deviance detection was evaluated by stimulus-specific adaptation index (SSAI), and the spontaneous burst-firing was estimated by total spike rate (TSR). SSAI was significantly decreased in the secondary response in exo-miRNA let-7b-treated cells. The intermittent spontaneous burst-firing was confirmed by the increase of TSR in neural circuitry after exposure of exo-miRNA let-7b. These results indicate that exo-miRNA let-7b holds the potential to decease auditory MMN leading to the generation of the spontaneous burst-firing in neural cells. Our results suggest that exo-miRNA let-7b might disrupt the sensory memory network in the auditory-brain, decreasing the special perception.
|
| Free Research Field |
内耳基礎研究
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究結果は、 内耳細胞の過興奮性細胞死を引き起こすmiRNA let-7bが認知症等の神経障害における耳鳴あるいは脳過敏反応の原因となる可能性を示唆している。即ち、miRNAlet-7bは、臨床的に聴覚中枢制御機能低下による耳鳴バイオマーカーとして有用であることを意味している。また、エクソソームは細胞への親和性も高く高率に細胞移入可能であり、miRNAlet-7b 阻害剤は耳鳴中枢制御機能をターゲットとした新規治療薬 になり得る。本研究は、客観的な評価法・的確な治療法のない耳鳴で苦しむ多くの患者にとって大きな意義がある。
|
