The Effect of ATP on Neurotrophic Factors in Olfactory Epithelium of Neonate Mice
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Mammalian olfactory epithelium (OE) has the unique ability to remain functional even after extensive and repetitive damage by continually replacing damaged cells. Past studies suggest that extracellular ATP and neurotrophic factors increase the rate at which OE cells are replaced. This study tested the hypothesis that extracellular ATP causes the release of neurotrophic factors transforining growth factor alpha (TGF-α) and basic fibroblast growth factor (FGF2) in OE. Neonate mouse OE tissue slices were incubated in nine different media solutions including purinegic receptor agonists and/or purinergic receptor antagonists. FGF2 and TGF-α immunoassays were run with media collected. TGF-α immunoassay did not indicate that ATP increased TGF-α release, however FGF2 immunoassays revealed a significant increase in FGF2 release. To determine the cell type that expresses TGF-α and FGF2, neonatal mice were intranasally instilled with ATP or Ringer's solution, and tissue was collected for immunohistochemisty. Immunohistochemistry confirmed FGF2 expression was greater in mice with ATP treatment than Ringer's treatment. Minimal expression of TGF -α was visible in mice treated with both ATP and saline. Our data show that ATP upregulate expression and stimulates the release ofFGF2, but not TGF-α. Collectively, these data suggest that ATP may play a role in the regeneration of the olfactory epithelium by evoking the synthesis and release of neurotrophic factor FGF2 .