Reversal of Olfactory Disturbance in Allergic Rhinitis Related to OMP Suppression by Intranasal Budesonide Treatment

PURPOSE: We evaluated the severity of olfactory disturbance (OD) in the murine model of allergic rhinitis (AR) and local allergic rhinitis (LAR) in mice. We also investigated the therapeutic effect of an intranasal steroid on OD. METHODS: Forty BALB/c mice were divided into 5 groups (n = 8 for each). The control group was sensitized intraperitoneally (i.p.) and challenged intranasally (i.n.) with saline. Mice in the AR group got i.p. and i.n. ovalbumin (OVA) administration for AR induction. The LAR group was challenged i.n. with 1% OVA for inducing local nasal allergic inflammation, without inducing the systemic allergy. The OD group got an i.p. methimazole administration (75 mg/kg) to induce total destruction of olfactory mucosa. Mice in the intranasal budesonide group received i.n. budesonide (12.8 μg per time, 30 minutes after the i.n. OVA challenge) while using OVA to cause systemic allergies. We conducted a buried-food pellet test to functionally assess the degree of OD in each group by measuring the time taken until finding hidden food. We evaluated the damage to olfactory epithelium using histopathologic evaluation and compared the degree of olfactory marker protein (OMP) expression in olfactory epithelium using immunofluorescent staining. RESULTS: Mice of the AR (81.3 ± 19.8 seconds) and LAR groups (66.2 ± 12.7 seconds) spent significantly more time to detect the pellets than the control group (35.6 ± 12.2 seconds, P < 0.01). After treatment, the intranasal budesonide group exhibited significantly better results (35.8 ± 11.9 seconds) compared with the AR and LAR groups (P < 0.01). The AR and LAR groups showed considerable olfactory epithelial damage and suppression of OMP expression compared with the control group. In the intranasal budesonide group, the olfactory lesions and OMP expression had improved substantially. CONCLUSIONS: OD may be caused by olfactory epithelial damage and suppression of OMP expression in nasal allergic inflammation and could be reversed using an intranasal steroid.

Gene Expression Profile of Olfactory Transduction Signaling in an Animal Model of Human Multiple Sclerosis

Olfactory dysfunction occurs in multiple sclerosis in humans, as well as in an animal model of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyze differentially expressed genes (DEGs) in olfactory bulb of EAE-affected mice by next generation sequencing, with a particular focus on changes in olfaction-related signals. EAE was induced in C57BL/6 mice following immunization with myelin oligodendrocyte glycoprotein and adjuvant. Inflammatory lesions were identified in the olfactory bulbs as well as in the spinal cord of immunized mice. Analysis of DEGs in the olfactory bulb of EAE-affected mice revealed that 44 genes were upregulated (and which were primarily related to inflammatory mediators), while 519 genes were downregulated; among the latter, olfactory marker protein and stomatin-like 3, which have been linked to olfactory signal transduction, were significantly downregulated (log2 [fold change] >1 and p-value < 0.05). These findings suggest that inflammation in the olfactory bulb of EAE-affected mice is associated with the downregulation of some olfactory signal transduction genes, particularly olfactory marker protein and stomatin-like 3, which may lead to olfactory dysfunction in an animal model of human multiple sclerosis.

Experimental research of the olfactory receptor neurons of olfactory dysfunction by allergic rhinitis / 中国耳鼻咽喉头颈外科

OBJECTIVE To set up an intranasal ovalbumin-induced animal model of allergic rhinitis(AR) accompanied with olfactory dysfunction in mice. By observing the olfactory pathway in mice using manganese-enhanced magnetic resonance imaging (MEMRI) and the relatively morphologic structural and immunological changes in olfactory epithelium, the influence of AR on olfactory receptor neurons(ORNs) was studied.METHODS Forty SD mice were randomly divided into two groups, the research group(n=30) and the control group(n=10). The research group was intraperitoneally injected and intranasal application of ovalbumin to establish an AR mice model. The olfactory function of the mice was evaluated by buried food test(BFT). ELISA was performed to measure the level of IgE in serum. MEMRI images were acquired with a 7.0 T micro-MR scanner. HE staining and immunohistochemistry were used to observe the tissues morphology change of olfactory mucosa and OMP expression.RESULTS The olfactory function evaluation of the AR mice model indicated that the incidence of olfactory dysfunction in AR mice was 40.0%. The AR mice with olfactory dysfunction had no signal enhancement in MEMRI. The olfactory epithelium became thinner, layer numbers of ORNs were decreased with disorder arrangement and the OMP expression was decreased in AR mice with olfactory dysfunction compared with that in AR mice without olfactory dysfunction(P=0.018) and the control group(P=0.0141).CONCLUSION An animal model of AR accompanied with olfactory dysfunction in mice was successfully established. The influence of AR on ORNs and thus cause the change of the olfactory pathway is one of the major pathogenesis of olfactory dysfunction in AR.

Compound Betamethasone enhances the expression of olfactory marker protein in olfactory mucosa of mice injured by influenza virus / 基础医学与临床

Objective To investigate the effects of compound Betamethasone on the expression of olfactory marker protein(OMP)in murine olfactory mucosa injured by influenza virus.Methods An animal model was developed by intranasal application of influenza virus to mice.Compound Betamethasone was injected i.p.(3.5 mg/kg)on day 2 and day 4 after the insult.The expression of OMP was tested by immunohistochemistry and Western blot.Results The expression of OMP was significantly downregnlated in the olfactory mucosa of influenza virus control group 1 and influenza virus control group 2;the expression of OMP was significantly upregulated in the olfactory mucosa of post-infection compound Betamethasone group 1 and post-infection compound Betamethasone group 2.Conclusion Compound Betamethasone can enhance the expression of OMP in the olfactory mucosa injured by influenza virus.

Histopathological Changes of Olfactory Epithelium in the Rats Exposed to Cigarette Smoke / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Although exposure to cigarette smoke has been reported to be associated with olfactory dysfunction, the pathophysiology is poorly understood. The purpose of this study is to evaluate the histopathological change of olfactory epithelium according to exposure duration of cigarette smoke and to investigate the effects of cigarette smoke on the olfactory epithelium. SUBJECTS AND METHOD: Thirty-six healthy Sprague-Dawley rats were divided into 2 groups. Experimental groups (n=28) were exposed to cigarette smoke during 2.5 hours (total 5 cigarettes) per one day for 5 days, 11 days and 3, 4, 5, 6, 9 weeks. Control group (n=8) was placed at the same room without smoke exposure and sacrificed at 4 and 9 weeks. Histopathological changes of olfactory epithelium through light microscope and immunohistochemistric findings of olfactory marker protein (OMP) through confocal microscope were observed. The numbers of cells in olfactory epithelium were counted at each period. RESULTS: From 5 days of cigarette smoke exposure, defection of epithelial cells, random arrangement of olfactory receptor cells and decreased thickness of olfactory epithelium were noticed. Numbers of olfactory receptor cells were significantly decreased at 11 days and 3 weeks after smoke exposure, and this finding of decreased number of olfactory receptor cells were continued until 9 weeks of exposure. Numbers of OMP-positive olfactory receptor cells were continuously decreased according to exposure duration. CONCLUSION: The olfactory epithelial cells could be directly affected by cigarette smoke. The numbers of olfactory epithelial cells including olfactory receptor cells were continuously decreased until 9 weeks after cigarette smoke exposure.