Molecular and cellular bases for cigarette smoke-induced impairments of olfactory neurogenesis

2018 Fiscal Year Final Research Report

• 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
• Keywords: タバコ煙 / 嗅神経上皮 / 嗅覚障害 / 加齢 / 嗅粘膜

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.

Free Research Field

耳鼻咽喉科

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。