Immunolocalization of retinoic acid receptors in the mammalian olfactory system and the effects of olfactory denervation on receptor distribution

All-trans retinoic acid (ATRA), a metabolite of vitamin A, binds to retinoic acid receptors (RARs) to mediate gene transcription in target cells. We previously found that an ATRA supplement enhanced olfactory recovery rate in adult mice after olfactory bulb deafferentation. In this study, we examined the cellular localization of RARα, RARβ, and RARγ and the effects of surgery and ATRA treatment using immunocytochemistry. Mice received a left olfactory nerve transection with the right side serving as internal control. One day after surgery, the mice were given either ATRA mixed with sesame oil or just sesame oil. In the unoperated olfactory bulb, only RARα immunoreactivity (ir) was observed. In the unoperated right olfactory epithelium, RARα-ir was found in flask-shaped cells located in the supporting cell layer, in cell clusters above the basal cell layer, in cells in the lamina propria, in some respiratory cells and in the olfactory bulb. The flask-shaped cells did not immunostain for either neurons or sustentacular cells. RARβ-ir was localized only in the respiratory cells while no RARγ-ir was observed in the olfactory epithelium. The density of RARα-ir cells was higher in the operated left olfactory epithelium and highest after ATRA treatment. This study demonstrates the presence of RARs in the olfactory system, provides additional support that the ATRA-signaling pathway may be involved in the recovery of the olfactory epithelium after injury, and suggests a role for an unstudied cell type in that process.