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

• Published in: Cell and tissue research Vol. 378; no. 2; pp. 175 - 193
• Main Authors: Iwamura, Hitoshi, Kondo, Kenji, Kikuta, Shu, Nishijima, Hironobu, Kagoya, Ryoji, Suzukawa, Keigo, Ando, Mizuo, Fujimoto, Chisato, Toma-Hirano, Makiko, Yamasoba, Tatsuya
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2019; Springer; Springer Nature B.V
• Subjects: Animals; Basal cells; Biomedical and Life Sciences; Biomedicine; Brain architecture; Caloric Restriction - adverse effects; Cell Proliferation; Chemokines; Dietary restrictions; DNA microarrays; Gene expression; Human Genetics; Inflammation; Interleukin 6; Interleukin-6 - metabolism; Ki-67 Antigen - metabolism; Male; Methimazole; Mice; Mice, Inbred C57BL; Molecular Medicine; Mucosa; Nerve Regeneration; Odorant receptors; Olfactory epithelium; Olfactory marker protein; Olfactory Marker Protein - metabolism; Olfactory Mucosa - cytology; Olfactory Mucosa - injuries; Olfactory receptor neurons; Olfactory Receptor Neurons - cytology; Olfactory Receptor Neurons - physiology; Polymerase chain reaction; Proteomics; Regeneration; Regular Article; Cell proliferation; DNA microarray; Olfactory neuroepithelium; Caloric restriction; Interleukin-6
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-019-03047-1

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.