Age-related olfactory dysfunction: cellular and molecular characterization in the rat.

David B Conley; Alan M Robinson; Michael J Shinners; Robert C Kern

PubMed · 12862407

Age-related olfactory dysfunction: cellular and molecular characterization in the rat.

David B Conley·Alan M Robinson·Michael J Shinners·Robert C Kern

Abstract

BACKGROUND: Olfactory receptor neurons (ORNs) undergo apoptosis at a baseline rate even in the absence of obvious disease. Although the precise triggers of the apoptotic cascade are unclear, ORNs are exposed directly to the external environment, making them susceptible to injury. As an adaptive mechanism, mammals have the ability to replace lost ORNs throughout adult life from neuronal precursors within the olfactory epithelium (OE). In humans, this process fails with age as the surface area of the OE and the number of ORNs decline, coupled with a loss of clinical olfactory function. The question addressed in this study is whether this age-related failure of olfactory sensation is a result of a decrease in neuronal proliferation or an increase in ORN cell death. METHODS: To begin to address this question the ribonuclease protection assay was used to assess expression of apoptosis-related genes in rat OE as a function of age. Second, the terminal deoxynucleotide transferase end labeling assay was used to assess the percentage of ORNs undergoing apoptosis (apoptotic index) in three groups of animals: young (12 weeks), old (32 months), and bulbectomized rats. Bulbectomy is a standard model for ORN injury associated with a massive increase in ORN apoptosis and serves as a positive control. RESULTS: Ribonuclease protection assay data indicate an age-related increase in Bax, Bcl-xL, and procaspase-3 messenger RNA expression in aged compared with young rats. A similar but more pronounced increase in expression of these apoptotic-related genes is seen after bulbectomy. The terminal deoxynucleotide transferase end labeling assay also showed a statistically significant increase in the apoptotic index with both age and bulbectomy. CONCLUSION: Taken together, the current results indicate that aging and injury induce parallel changes in OE. Furthermore, these findings support the hypothesis that age-related olfactory dysfunction is, at least in part, related to an increase in ORN cell death.

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Aging Animals DNA-Binding Proteins Gels In Situ Nick-End Labeling Male Olfaction Disorders Olfactory Bulb RNA Rats Rats, Inbred F344 Replication Protein A Ribonucleases Smell Journal Article Research Support, Non-U.S. Gov't

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David B Conley, Alan M Robinson, Michael J Shinners, Robert C Kern. Age-related olfactory dysfunction: cellular and molecular characterization in the rat.. https://pubmed.ncbi.nlm.nih.gov/12862407/

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