Cell death in the olfactory epithelium

In the nervous system of vertebrates the olfactory epithelium presents unique cytological characteristics. In the olfactory mucosa, olfactory neurons die and are replaced from undifferentiated neuroblasts over the entire life span of the animal. It remains unclear whether these neurons die as a result of a direct insult from the environment or in fulfillment of a physiological program of cell death. We have studied the distribution and the characteristics of cell death in the olfactory epithelium of normal, adult rats. The olfactory epithelium contains pycnotic bodies resembling those described for thymocytes undergoing terminal apoptotic changes. These appear at all levels in the epithelium, under both light and electron microscopes and can also be demonstrated after vital staining with acridine orange. Chromatin condensation into large blocks, often located at the nuclear periphery, is a morphological hallmark of the nuclei of mature olfactory neurons, which also present an increase in electron density of the cytoplasm. After non-radioactive in situ labeling of fragmented DNA, the nuclei of olfactory neurons are positive. Under the same reaction conditions (mild protease digestion), most of the nuclei of the supporting and basal cells are negative. In vivo incorporation of 5-bromouridine, a marker of RNA synthesis, is also lower in olfactory neurons than in basal and supporting cells. These findings suggest that olfactory neurons are committed very early to physiological cell death.