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Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice

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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.

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Acknowledgments

We are deeply grateful to Dr. Francis H.W. Shand for editorial assistance in preparing this article.

Funding

This work was supported by a Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (No. 24791749) and by the Smoking Research Foundation (Tokyo, Japan).

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Authors and Affiliations

  1. Department of Otolaryngology, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan

    Rumi Ueha, Takashi Sakamoto, Hironobu Nishijima, Shu Kikuta, Kenji Kondo & Tatsuya Yamasoba

  2. Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0033, Japan

    Satoshi Ueha & Kouji Matsushima

  3. Department of Otolaryngology, Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Kotobashi Sumida-ku, Tokyo, 130-8575, Japan

    Kaori Kanaya & Keigo Suzukawa

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  1. Rumi Ueha
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  2. Satoshi Ueha
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  4. Kaori Kanaya
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  5. Keigo Suzukawa
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Correspondence to Rumi Ueha.

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Ueha, R., Ueha, S., Sakamoto, T. et al. Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice. Neurotox Res 30, 213–224 (2016). https://doi.org/10.1007/s12640-016-9617-5

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  • DOI: https://doi.org/10.1007/s12640-016-9617-5

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