Dorsal-zone-specific reduction of sensory neuron density in the olfactory epithelium following long-term exercise or caloric restriction

Ayinuer Tuerdi,Kenji Kondo,Makoto Kinoshita,Shu Kikuta,Teru Kamogashira,Tatsuya Yamasoba,Shinichi Iwasaki

doi:10.1038/s41598-018-35607-w

Ayinuer Tuerdi, Kenji Kondo + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-35607-w

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Journal: Scientific Reports	Publication Date: Nov 23, 2018
Citations: 11	License type: open-access

Affiliation: The University of Tokyo

Abstract

Exercise (Ex) and caloric restriction (CR) reduce oxidative stress and improve organ function. For instance, voluntary Ex or CR is known to reduce age-related cochlear damage in male C57BL/6J mice. However, the effect of Ex and CR on the olfactory system is unknown. In this study, we confirmed the positive effect of Ex and CR on age-related cochlear damage, but found that Ex and CR affected negatively cell dynamics in the olfactory epithelium (OE) by reducing the number of mature olfactory sensory neurons (OSNs) and increasing the number of proliferative basal cells and apoptotic OSNs in the dorsal zone of the olfactory epithelium (OE), which contains neurons expressing NADPH quinone oxido-reductase 1 (NQO1). In addition, these interventions resulted in lower odor-induced c-fos expression in areas of the olfactory bulb receiving projections from dorsal-zone OSNs than in areas receiving ventral-zone projections. Further, we observed substantial oxidative stress in NQO1-positive cells and apoptotic OSNs in the dorsal zone in Ex and CR animals. These results suggest that, in contrast to their positive effects in other organs, Ex and CR facilitate oxidative stress and negatively impact structure and function in dorsal-zone OSNs, probably in association with NQO1 bioactivation.

Highlights

Oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses
Body-weight increase in mice in the experimental groups was significantly lower than that in their age-matched controls [(5 months: Ex, p < 0.001; caloric restriction (CR), p < 0.001) (10 months: Ex, p < 0.001; CR, p < 0.001) (Mann-Whitney U test; Fig. 1e)]. These results suggest that Ex and CR reduce body-weight gain, which can influence metabolic energy systems
The percentages of anti-8-hydroxy-2′-deoxyguanosine (8-OHdG)-positive spiral ganglion cells (SGCs) cells in Ex and CR mice were significantly lower than those in control mice [8-OHdG in the basal turn: Ex, p = 0.12; CR, p = 0.8) (8-OHdG in the apical turn: Ex, p < 0.001; CR, p < 0.001) (n = 3 mice per group; Mann-Whitney U test; Fig. 2g,h)]. These results indicate that Ex and CR reduced the age-related degeneration of the outer HC (OHC) and the SGC and reduced oxidative stress in the SGC in the apical regions of the cochlea

Summary

Introduction

Oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses. Long-term exercise (Ex) and caloric restriction (CR) are considered robust non-genetic methods for reducing oxidative stress in many organs[3,4]. These interventions can reduce body weight, systemic insulin/insulin-like growth factor (IGF) signaling, the basal rate of mitochondrial hydrogen peroxide production in tissue, and inflammation. The regeneration process, as well as through changes in energy metabolism and the production of metabolic byproducts at the cellular level[8,9] These observations suggest that Ex and CR interventions affect the homeostasis of cell dynamics in the OE. Declines in auditory function are associated with loss of hair cells (HCs), but Ex and CR delayed the age-related degeneration of HCs2

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