Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium
Chronic 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00050/full |
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| author | Umberto Crisafulli Umberto Crisafulli André M. Xavier Fabiana B. dos Santos Tavane D. Cambiaghi Seo Y. Chang Marimélia Porcionatto Beatriz A. Castilho Bettina Malnic Isaias Glezer |
| author_facet | Umberto Crisafulli Umberto Crisafulli André M. Xavier Fabiana B. dos Santos Tavane D. Cambiaghi Seo Y. Chang Marimélia Porcionatto Beatriz A. Castilho Bettina Malnic Isaias Glezer |
| author_sort | Umberto Crisafulli |
| collection | DOAJ |
| description | Chronic 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 (DEX; 200 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. |
| first_indexed | 2024-04-13T15:07:01Z |
| format | Article |
| id | doaj.art-e9208f48be2c4127a8e5fbbd38f20a3b |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T15:07:01Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-e9208f48be2c4127a8e5fbbd38f20a3b2022-12-22T02:42:07ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-03-011110.3389/fnmol.2018.00050335511Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory EpitheliumUmberto Crisafulli0Umberto Crisafulli1André M. Xavier2Fabiana B. dos Santos3Tavane D. Cambiaghi4Seo Y. Chang5Marimélia Porcionatto6Beatriz A. Castilho7Bettina Malnic8Isaias Glezer9Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, BrazilDepartment of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, BrazilDepartment of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilChronic 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 (DEX; 200 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.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00050/fullanosmiainflammationcorticoidsinnate immune responseneurogenesisneuronal cell death |
| spellingShingle | Umberto Crisafulli Umberto Crisafulli André M. Xavier Fabiana B. dos Santos Tavane D. Cambiaghi Seo Y. Chang Marimélia Porcionatto Beatriz A. Castilho Bettina Malnic Isaias Glezer Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium Frontiers in Molecular Neuroscience anosmia inflammation corticoids innate immune response neurogenesis neuronal cell death |
| title | Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_full | Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_fullStr | Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_full_unstemmed | Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_short | Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium |
| title_sort | topical dexamethasone administration impairs protein synthesis and neuronal regeneration in the olfactory epithelium |
| topic | anosmia inflammation corticoids innate immune response neurogenesis neuronal cell death |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00050/full |
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