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Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice
Rumi Ueha1, Satoshi Ueha2, Takashi Sakamoto3
1Department of Otolaryngology, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. ruu1025@yahoo.co.jp.
Abstract:
The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest 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.
Insights
Cigarette smoke solution (CSS) hinders olfactory receptor neuron (ORN) regeneration after injury by impairing immature ORN development. This occurs partly by reducing insulin-like growth factor-1 (IGF-1) levels, suggesting IGF-1 is crucial for olfactory system repair.
Area of Science:
- Neuroscience
- Regenerative Medicine
Background:
- The mammalian olfactory system can regenerate olfactory receptor neurons (ORNs).
- Cigarette smoking is a known cause of olfactory dysfunction, but its impact on ORN regeneration is unclear.
Purpose of the Study:
- To investigate how cigarette smoke affects ORN regeneration after injury.
- To elucidate the mechanisms underlying cigarette smoke-induced impairment of ORN repair.
Main Methods:
- Methimazole was used to induce ORN injury and olfactory dysfunction in mice.
- Mice received intranasal administration of cigarette smoke solution (CSS).
- ORN regeneration, progenitor cell activity, and neurotrophic factor expression were analyzed.
Main Results:
- CSS suppressed ORN and olfactory recovery following injury.
- CSS impaired the development of immature ORNs (GAP43+) but not ORN progenitors (SOX2+).
- CSS reduced injury-induced insulin-like growth factor-1 (IGF-1) expression, and IGF-1 administration restored ORN recovery.
Conclusions:
- Cigarette smoke impairs ORN regeneration by inhibiting the maturation of immature ORNs.
- Reduced IGF-1 levels in the nasal mucosa contribute to CSS-induced suppression of ORN repair.
- IGF-1 is essential for effective olfactory receptor neuron regeneration after injury.
