Elsevier

Neuroscience

Volume 131, Issue 3, 2005, Pages 733-743
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2004.11.011Get rights and content

Abstract

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.

Section snippets

Animal subjects

Fifty-four male Swiss Webster mice ranging in age from 8–10 weeks were purchased from Charles River Laboratories (Wilmington, MA, USA) and housed individually in standard plastic cages under a 12-h light/dark cycles. The mice were given food and water ab libitum. All surgical and treatment procedures were conducted in accordance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals. The Institutional Animal Care and Use Committee at the Monell Center approved the

Localization of RARs-ir in the adult mouse olfactory system

Fig. 1 shows the cellular localization of RARα, RARβ, and RARγ in the unoperated side of the olfactory system of post-surgical day 2 mice given oil. In the respiratory epithelium, both RARα-ir (Fig. 1A, B) and RARβ-ir (Fig. 1C, D) were observed in some respiratory cells, whereas no RARγ-ir was observed (Fig. 1E, F). In the OE of the septum, RARα-ir was observed in flask-shaped cells whose cell bodies were located in the supporting cell layer (Fig. 1G). A closer examination of an RARα-ir

Discussion

In this study, we have localized specific RAR proteins in several cell populations of the olfactory system of the adult mouse and found that olfactory denervation and ATRA treatment each induced a higher number of RARα-ir cells in the operated OE. These results, together with our previous behavioral findings, imply that the ATRA-signaling pathway is involved in regeneration and recovery of the OE in the adult olfactory system.

Acknowledgments

The authors thank Sarah Herman, Tatyana Dankulich, and Anna Demidova for their assistance in immunocytochemistry and Hakan Ozdener for his assistance with Western blot. The authors also thank Dr. Frank Margolis and Dr. James Schwob for generously providing antibodies. This study was supported by the National Institute on Deafness and Other Communication Disorders DC04645 (K.K.Y.), DC02876 and the National Science Foundation DBI-0216310 (N.E.R.).

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