期刊
AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
卷 24, 期 3, 页码 192-196出版社
SAGE PUBLICATIONS INC
DOI: 10.2500/ajra.2010.24.3460
关键词
GAP-43; inflammation; markers; NCAM; olfaction; OMP; rhinosinusitis; TNF; transgenic
资金
- NIDCD NIH HHS [R01 DC009026-02, R01 DC009026, R01 DC009026-03, R01 DC009026-01A1] Funding Source: Medline
Background: Chronic rhinosinusitis (CRS) is among the most common causes of olfactory loss. The loss of the sense of smell is thought to result from structural and functional changes occurring in the olfactory epithelium caused by inflammation. However, the cellular mechanisms underlying CRS-associated olfactory loss remain incompletely understood. Methods: Transgenic mice expressing TNF-alpha specifically within the olfactory epithelium were used as a model for CRS-associated olfactory loss. TNF-alpha expression was induced over different time intervals, and olfactory epithelial tissue was assessed for the expression of neuronal markers by laser scanning confocal microscopy and Western blot. Results: TNF-alpha expression results in an inflammatory infiltrate in the olfactory epithelium, thinning of the olfactory neuron layer, and a progressive loss of olfactory function. Reduced expression of markers for neurons and mature olfactory neurons (neural cell adhesion molecule [NCAM] and olfactory marker protein [OMP], respectively) was observed in the neuroepithelium and in the subepithelial axon bundles. Expression of growth-associated protein (GAP) 43, a marker for immature neurons, was also reduced. These alterations were reversed when TNF-alpha expression was discontinued. Conclusion: TNF-alpha expression in a transgenic model of CRS-associated olfactory loss results in progressive loss of olfactory neurons. Decreased GAP-43 expression suggests that TNF-alpha-associated inflammation inhibits differentiation of progenitor cells into immature olfactory neurons. Therefore, reduced regeneration of olfactory neurons may he an important mechanism underlying olfactory loss in CRS, in addition to neuronal loss or apoptosis. This mouse model represents a potential tool in the development of novel therapeutic strategies for the prevention of olfactory neuron loss in CRS. (Am J Rhinol Allergy 24, 192-196, 2010; doi: 10.2500/ajra.2010.24.3460)
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