Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium

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dc.citation.volumev. 11
dc.contributor.authorCrisafulli, Umberto [UNIFESP]
dc.contributor.authorXavier, Andre Machado [UNIFESP]
dc.contributor.authorSantos, Fabiana B. dos [UNIFESP]
dc.contributor.authorCambiaghi, Tavane David [UNIFESP]
dc.contributor.authorChang, Seo Y. [UNIFESP]
dc.contributor.authorPorcionatto, Marimélia Aparecida [UNIFESP]
dc.contributor.authorCastilho, Beatriz Amaral de [UNIFESP]
dc.contributor.authorMalnic, Bettina
dc.contributor.authorGlezer, Isaias [UNIFESP]
dc.coverageLausanne
dc.date.accessioned2020-07-20T16:31:16Z
dc.date.available2020-07-20T16:31:16Z
dc.date.issued2018
dc.description.abstractChronic inflammatory process in the nasal mucosa is correlated with poor smell perception. Over-activation of immune cells in the olfactory epithelium (OE) is generally associated with loss of olfactory function, and topical steroidal anti-inflammatory drugs have been largely used for treating such condition. Whether this therapeutic strategy could directly affect the regenerative process in the OE remains unclear. In this study, we show that nasal topical application of dexamethasone (DEXen
dc.description.abstract200 or 800 ng/nostril), a potent synthetic anti-inflammatory steroid, attenuates OE lesion caused by Gram-negative bacteria lipopolysaccharide (LPS) intranasal infusion. In contrast, repeated DEX (400 ng/nostril) local application after lesion establishment limited the regeneration of olfactory sensory neurons after injury promoted by LPS or methimazole. Remarkably, DEX effects were observed when the drug was infused as 3 consecutive days regimen. The anti-inflammatory drug does not induce OE progenitor cell death, however, disturbance in mammalian target of rapamycin downstream signaling pathway and impairment of protein synthesis were observed during the course of DEX treatment. In addition, in vitro studies conducted with OE neurospheres in the absence of an inflammatory environment showed that glucocorticoid receptor engagement directly reduces OE progenitor cells proliferation. Our results suggest that DEX can interfere with the intrinsic regenerative cellular mechanisms of the OE, raising concerns on the use of topical anti-inflammatory steroids as a risk factor for progressive olfactory function impairment.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Quim, Dept Biochem, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico
dc.description.sponsorshipCEPID Redoxoma
dc.description.sponsorshipIDFAPESP: 2007/53732-8
dc.description.sponsorshipIDFAPESP: 2013/07937-8
dc.description.sponsorshipIDFAPESP: 2011/13134-0
dc.description.sponsorshipIDFAPESP: 2009/04437-9
dc.description.sponsorshipIDFAPESP: 2016/24471-0
dc.description.sponsorshipIDFAPESP: 2009/52047-5
dc.description.sponsorshipIDFAPESP: 2010/50023-9
dc.description.sponsorshipIDCNPq: 484869/2012-4
dc.description.sponsorshipIDCNPq: 309860/2011-3
dc.description.sponsorshipIDCNPq: 478903/2012-0
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fnmol.2018.00050
dc.identifier.citationFrontiers In Molecular Neuroscience. Lausanne, v. 11, p. -, 2018.
dc.identifier.doi10.3389/fnmol.2018.00050
dc.identifier.fileWOS000426748200001.pdf
dc.identifier.issn1662-5099
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55836
dc.identifier.wosWOS:000426748200001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Molecular Neuroscience
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectanosmiaen
dc.subjectinflammationen
dc.subjectcorticoidsen
dc.subjectinnate immune responseen
dc.subjectneurogenesisen
dc.subjectneuronal cell deathen
dc.subjectS6 kinaseen
dc.subjectToll-like receptor 4en
dc.titleTopical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epitheliumen
dc.typeinfo:eu-repo/semantics/article
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