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Dexamethasone affects mouse olfactory mucosa gene expression and attenuates genes related to neurite outgrowth
Jun Tian1, Jayant M Pinto2, Yi Xin1
1Department of Otolaryngology-Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Background:
Olfaction is one of the important senses for humans. Systemic glucocorticoids are the most commonly used medications for olfactory loss because of their strong anti-inflammatory effects. However, their effect on olfactory function is still controversial and the precise mechanism is not clear. To gain a global view of the effect of systematic glucocorticoid treatment on gene expression in the olfactory mucosa (OM), we profiled these changes in a murine model of olfaction in order to identify underlying molecular mechanisms.
Methods:
C57BL/6 mice were injected daily for 2 weeks (WK2) with dexamethasone (DEX, intraperitoneally, 1 mg/kg body weight) vs 1 day of DEX (D1) vs controls, which received saline (Ctrl) (n = 9/group). Total RNA from the OM was used to analyze global gene expression. Genes showing changes in expression were compared using the Database for Annotation, Visualization and Integrated Discovery (DAVID, v6.7) and the General Olfactory Sensitivity Database (GOSdb; http://genome.weizmann.ac.il/GOSdb).
Results:
Between the WK2 and Ctrl groups, 3351 genes were differentially expressed, of which 236 genes were related to olfactory function. Genes involved in axon guidance, cell projection, and inflammation were enriched and overlapped significantly with those in the GOSdb.
Conclusion:
Systemic glucocorticoids exert effects on transcription of a notable number of genes in the OM and appear to orchestrate changes related to axon guidance, cell projection, and inflammation. Further examination may allow targeted therapies that lack the side effects of this category of medication.
Insights
Systemic glucocorticoid treatment impacts gene expression in the olfactory mucosa, affecting pathways crucial for olfactory function. This research clarifies molecular mechanisms underlying olfactory loss and treatment responses.
Area of Science:
- Neuroscience
- Genomics
- Pharmacology
Background:
- Olfaction is a vital human sense, but treatments for olfactory loss, like systemic glucocorticoids, have controversial efficacy and unclear mechanisms.
- Systemic glucocorticoids are widely used for olfactory dysfunction due to their anti-inflammatory properties.
- Understanding the molecular impact of these treatments on olfactory mucosa gene expression is critical.
Purpose of the Study:
- To investigate the global gene expression changes in the olfactory mucosa following systemic glucocorticoid treatment.
- To identify specific molecular pathways and genes affected by glucocorticoids in a murine model of olfaction.
- To elucidate the mechanisms underlying the therapeutic effects and potential side effects of glucocorticoids on olfactory function.
Main Methods:
- Gene expression profiling of olfactory mucosa from C57BL/6 mice treated with dexamethasone (DEX) for 2 weeks (WK2), 1 day (D1), or saline control (Ctrl).
- Analysis of global gene expression using RNA sequencing.
- Bioinformatic analysis of differentially expressed genes using DAVID and GOSdb.
Main Results:
- Significant differential expression of 3351 genes between WK2 and Ctrl groups.
- Identification of 236 genes directly related to olfactory function.
- Enrichment analysis revealed significant overlap in genes related to axon guidance, cell projection, and inflammation with olfactory databases.
Conclusions:
- Systemic glucocorticoids significantly alter gene transcription in the olfactory mucosa.
- These alterations involve pathways critical for axon guidance, cell projection, and inflammation, suggesting a role in olfactory function.
- Further research into these molecular mechanisms could lead to targeted therapies for olfactory disorders with fewer side effects.
