| Project/Area Number |
16K20231
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Otorhinolaryngology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Ueha Rumi 東京大学, 医学部附属病院, 助教 (10597131)
|
|---|
| Research Collaborator |
Ueha Satoshi
Kondo Kenji
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | タバコ煙 / 嗅神経上皮 / 嗅覚障害 / 加齢 / 嗅粘膜 / 喫煙 / 嗅上皮 / 再生 |
|---|
| Outline of Final Research Achievements |
Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms, by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs), remain unclear. To investigate whether cigarette smoke induces olfactory epithelial (OE) injury and olfactory dysfunction, we developed a mouse model of smoking with cigarette smoke solution (CSS). Then, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. In addition, we elucidated the aging and smoking effects on the OE and olfaction.
Our results suggest that ORN progenitors are targets of CSS-induced impairment of the OE, and that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa. In aged mice, increasing ORN death may result in continued reduction in the number of mature ORNs and olfactory dysfunction.
|
| Academic Significance and Societal Importance of the Research Achievements |
喫煙は嗅覚障害の主な原因の一つであるが，障害のメカニズムや禁煙による障害の改善に関する機序の多くは未解明であった。本研究では，タバコ煙溶液（CSS）による喫煙モデルマウスを用いてタバコ煙による嗅神経上皮障害のメカニズムを，次に，障害後の嗅神経上皮再生過程におけるCSSによる回復抑制の機序を解明した．さらに，加齢による嗅神経上皮への影響を詳細に解明した上で，加齢モデルではCSS投与による嗅神経上皮障は持続すること及びその分子生物学的背景を報告した．
本研究により，タバコ煙誘導性の嗅覚障害に関する機序の一部が解明され，炎症性サイトカイン抑制や細胞死の抑制が治療のターゲットであることが明らかになった。
|
