Background and Significance: Post-irradiation gustatory dysfunction is the loss of taste following radiation of the mouth for treatment of cancer. It is often accompanied by mucositis and xerostomia. Patients who experience loss of taste have a worse outcome compared to patients who retain their ability to taste and eat. Although the phenomenon is well described, the mechanism behind taste loss is unknown because of the incomplete understanding of the biology of the taste system. This study involves the development of an animal model to identify mechanisms underlying radiation-induced taste loss. The model allows measurement of changes in behavior and in neural activity of the chorda tympani, and couples them with histological changes in taste buds. The data derived from these studies will direct future human studies in validation and translational analysis.
Specific aim 1 a: To validate the effectiveness of the strontium tongue irradiator by demonstrating that the radiation damage is similar to that seen by whole-mouth irradiation methods, without the side effect of xerostomia and mucositis. 1b: To investigate how taste cell specific markers relate to taste cell turnover, both in the normal animal and during recovery following irradiation. The reappearance of specific cell types following irradiation recapitulates early development and thus taste cell lineage will be determined. Hypothesis: 1a: The strontium tongue irradiator produces the same degeneration and regeneration of taste buds seen by other methods of irradiation. 1b: Two taste cell lineages occur within the taste bud.
Specific aim 2 To examine the underlying neural mechanisms of irradiation- induced changes in taste function by directly recording from individual chorda tympani nerves in the presence of different tastants. Hypothesis: Chorda tympani nerves in irradiated animals require higher concentrations of stimuli to produce the same response seen in normal rats.
Specific aim 3 : The time course of degeneration and regeneration of specific subpopulations of taste cells following irradiation will be correlated with the measured behavioral changes. Hypothesis: The loss of taste perception induced by radiation is due to the loss of a selected subpopulation of taste cells, which are preferentially affected prior to the loss of the entire bud.
