The chorda tympani (CT) is susceptible to damage during dental procedures and inner ear surgeries (Bartoshuk et al., 2005). While reinnervation can occur in humans after damage to the CT nerve at either location, perceptual changes often persist despite the reappearance of taste buds. Peripheral nerve lesions in other systems result in central degenerative terminals and fibers that are first accompanied by glial reactions, particularly microglial responses (Aldskogius et al., 1985). Recently, peripheral damage to the CT showed morphological changes in the brainstem (Reddaway and Hill, 2007). This proposal aims to investigate glial alterations in the first central gustatory relay, the nucleus of the solitary tract (NTS), following peripheral damage to the CT. First, the time course and origin of the microglial response will be established. The time course will be quantified using immunostaining and morphometric cell counts as a measure of the microglial response. Preliminary studies showed and increased number of microglia on the injured side of the NTS. Microglia can proliferate locally and precursor cells can be recruited from the bone marrow at the periphery and differentiate into microglia. Bone marrow-chimeric mice allow for differentiation between peripherally derived and native cells in the NTS. These chimeric mice have GFP labeled bone marrow. Hence, any cell with GFP immunoreactivity is known to be of peripheral origin. In uninjured animals, almost no GFP label is detected in the NTS. BrdU, the thymidine analogue, will be administered and detected as a measure of microglia proliferation. Second, geniculate ganglia will be examined for cell death after nerve injury as a possible trigger for a microglial response. The possibility of transganglionic degeneration, in which cell bodies remain intact but central processes degenerate, will also be studied in the NTS using measurements of CT volume in the NTS as well as EM analysis. Finally, to test the hypothesis the microglial response is necessary for the morphological changes in the brainstem observed post CT injury, treatment with Minocycline will be used to dampen the microglial response after CT injury. Brainstem morphology will be compared after CT injury between microglial attenuated groups and normal microglial response groups.
|Ganchrow, Donald; Ganchrow, Judith R; Cicchini, Vanessa et al. (2014) Nucleus of the solitary tract in the C57BL/6J mouse: Subnuclear parcellation, chorda tympani nerve projections, and brainstem connections. J Comp Neurol 522:1565-96|
|Bartel, Dianna L (2012) Glial responses after chorda tympani nerve injury. J Comp Neurol 520:2712-29|