Human psychophysical studies demonstrate a clear decline in olfactory sensation as a function of age, associated with a concomitant loss of peripheral receptor neurons. This sensory deficit in the elderly may contribute to nutritional problems, diminished quality of life as well as potential environmental safety concerns. The decline in olfactory ability occurs despite the fact that the mammalian olfactory epithelium retains the capacity to regenerate neurons lost as a result of injury, into adult life. The central question is whether this reduction in neuronal number reflects an age-related decline in proliferation or regeneration, or both. The current study will examine the effects of aging on the normal and injured (bulbectomized) rat olfactory epithelium. Removal of the olfactory bulbs or bulbectomy, is the standard injury model for the olfactory epithelium, resulting in a well-established synchronous wave of apoptotic neuronal cell death, followed by attempts at regeneration. Since the end-organ has been removed, newly generated receptor neurons are, themselves ultimately fated to undergo apoptosis. Specifically, this proposal will utilize the TUNEL assay to quantify the extent of normal and post-bulbectomy olfactory apoptosis as a function of age. Experimental analyses will be performed on normal and 9 day post-bulbectomy animals, since, by that time the injured epithelium consists of a relatively uniform population of regenerating neurons. These studies will begin to address this central hypothesis: that newly generated receptor neurons in the aged animal are predisposed to undergo apoptosis in comparison to neurons generated in their younger counterparts.
| Kern, R C; Conley, D B; Haines 3rd, G K et al. (2004) Treatment of olfactory dysfunction, II: studies with minocycline. Laryngoscope 114:2200-4 |
| Kern, R C; Conley, D B; Haines 3rd, G K et al. (2004) Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunction. Laryngoscope 114:279-85 |
