Abstract
Introduction: Exposure to cigarette smoke is a cause of olfactory dysfunction. We previously reported that in young mice, cigarette smoke damaged olfactory progenitors and decreased mature olfactory receptor neurons (ORNs), then, mature ORNs gradually recovered after smoking cessation. However, in aged populations, the target cells in ORNs by cigarette smoke, the underlying molecular mechanisms by which cigarette smoke impairs the regenerative ORNs, and the degree of ORN regeneration after smoking cessation remain unclear.Objectives: To explore the effects of cigarette smoke on the ORN cell system using an aged mouse model of smoking, and to investigate the extent to which smoke-induced damage to ORNs recovers following cessation of exposure to cigarette smoke in aged mice.Methods: We intranasally administered a cigarette smoke solution (CSS) to 16-month-old male mice over 24 days, then examined ORN existence, cell survival, changes of inflammatory cytokines in the olfactory epithelium (OE), and olfaction using histological analyses, gene analyses and olfactory habituation/dishabituation tests.Results: CSS administration reduced the number of mature ORNs in the OE and induced olfactory dysfunction. These changes coincided with an increase in the number of apoptotic cells and Tumor necrosis factor (TNF) expression and a decrease in Il6 expression. Notably, the reduction in mature ORNs did not recover even on day 28 after cessation of treatment with CSS, resulting in persistent olfactory dysfunction.Conclusion: In aged mice, by increasing ORN death, CSS exposure could eventually overwhelm the regenerative capacity of the OE, resulting in continued reduction in the number of mature ORNs and olfactory dysfunction.
Highlights
Exposure to cigarette smoke is a cause of olfactory dysfunction
We examined whether the OMP+ mature olfactory receptor neuron (ORN) population would recover after cessation of cigarette smoke solution (CSS) administration
A time course analysis revealed that the reduction in OMP+ ORN numbers continued even after cessation of CSS administration, and that the reduction became more severe on day 28 after the final intranasal administration of CSS (Figures 2A,B)
Summary
Exposure to cigarette smoke is a cause of olfactory dysfunction. We previously reported that in young mice, cigarette smoke damaged olfactory progenitors and decreased mature olfactory receptor neurons (ORNs), mature ORNs gradually recovered after smoking cessation. Aging-related olfactory dysfunction is associated with several histological changes in the olfactory neuroepithelium such as a thinning of the olfactory neuroepithelium (Weiler and Farbman, 1997; Watanabe et al, 2006; Kondo et al, 2009) and respiratory epithelial metaplasia (Paik et al, 1992; Nagano et al, 1997; Rosli et al, 1999). A part of the olfactory neuroepithelium in the elderly is converted into metaplastic respiratory epithelium and the metaplastic regions increase with age (Holbrook et al, 2011; Suzukawa et al, 2011). These morphological changes suggest that there is impairment in the regenerative function of ORNs in aged populations
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