Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa

  • Hitoshi Iwamura
  • Kenji KondoEmail author
  • Shu Kikuta
  • Hironobu Nishijima
  • Ryoji Kagoya
  • Keigo Suzukawa
  • Mizuo Ando
  • Chisato Fujimoto
  • Makiko Toma-Hirano
  • Tatsuya Yamasoba
Regular Article


The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured.


Caloric restriction Olfactory neuroepithelium Cell proliferation DNA microarray Interleukin-6 



We thank Yoshiro Mori, Yukari Kurasawa, Atsuko Tsuyuzaki, Kimiko Miwa, Koichi Miyazawa, Noriyuki Kondo and Kenzaburo Kondo for their technical assistance.


This work was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology (nos. 21791598, 23592506, 26293366; K. Kondo).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Animal Care and Use Committee of the University of Tokyo and conducted in accordance with the guidelines of the National Institute of Health for the Care and Use of Laboratory Animals.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hitoshi Iwamura
    • 1
  • Kenji Kondo
    • 1
    Email author
  • Shu Kikuta
    • 1
  • Hironobu Nishijima
    • 1
  • Ryoji Kagoya
    • 1
  • Keigo Suzukawa
    • 1
  • Mizuo Ando
    • 1
  • Chisato Fujimoto
    • 1
  • Makiko Toma-Hirano
    • 1
  • Tatsuya Yamasoba
    • 1
  1. 1.Department of Otolaryngology-Head and Neck SurgeryThe University of Tokyo Graduate School of MedicineTokyoJapan

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