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. 2022 Jan;26(1):198-203.
doi: 10.26355/eurrev_202201_27768.

Effects of chronic intranasal dantrolene on nasal mucosa morphology in mice

B Jiang  1 , Y Shi, M B Abou, L Xu, G Liang, H Wei
Affiliations

Effects of chronic intranasal dantrolene on nasal mucosa morphology in mice

B Jiang et al. Eur Rev Med Pharmacol Sci. 2022 Jan.

Abstract

Objective: We have previously shown that the intranasal administration of dantrolene ameliorated cognitive dysfunction in the 5XFAD mouse model of Alzheimer's disease. This study examines the morphology of the nasal mucosa after 10 months of intranasal dantrolene in 5XFAD mice.

Materials and methods: 5XFAD mice were either treated with intranasal dantrolene (5 mg/kg, 3 times/wk) from 2 months to 12 months of age or given no treatment at all. The mice were euthanatized at 12 months of age and the snouts were processed for histological examination. The morphology of the nasal mucosa was assessed and compared between the two groups.

Results: There were no significant differences in the thickness of the olfactory epithelium or the proportion of the thickness of the glandular layer to the wall of mucosa and submucosa in the nasal passages.

Conclusions: Long-term intranasal administration of dantrolene did not significantly change the nasal mucosa morphology in 5XFAD mice.

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Conflict of interest statement

Conflict of Interest

Drs. Huafeng Wei and Ge Liang are listed as inventors of a US provisional patent application entitled “Intranasal Administration of Dantrolene for Treatment of Alzheimer’s Disease” filed on June 28, 2019 (Serial number 62/868,820) by the University of Pennsylvania Trustee. The provisional patent application is also part of the research collaboration agreement between the University of Pennsylvania and Eagle Pharmaceuticals, Inc., which produces and sells a new formula of dantrolene (Ryanodex) for the treatment of malignant hyperthermia. Dantrolene used in this study was purchased from Sigma Company, USA. Other authors declare that they have no conflict of interest.

Figures

Figure 1.
Figure 1.
Representative H&E-stained slide images of the nasal cavity from control and intranasal dantrolene treatment groups in 5XFAD mice. Coronal sections of representative mouse nasal passages from the control group (A, CON, n = 4) and the intranasal dantrolene treatment group (B, IN-DAN, n = 4), stained with Hematoxylin and Eosin, illustrating the nasal anatomy. Higher magnification focused on the dorsal meatus (DM) as indicated in A and B (dashed blocks) are presented in C (CON) and D (IN-DAN), respectively. Nt, nasoturbinate; S, nasal septum; OE, olfactory epithelium; RE, respiratory epithelium. In CON, nothing was administrated via the intranasal route. Intranasal administration of dantrolene was administered 3 times per week from 2 months to 12 months of age in IN-DAN. Scale bars: 200 μm (A, B); 100 μm (C, D).
Figure 2.
Figure 2.
Intranasal dantrolene treatment did not change the nasal mucosal membrane thickness. Representative Hematoxylin and Eosin stained images (A) control group (CON); (B) intranasal dantrolene treatment group (IN-DAN)) are presented to illustrate the morphometric measurements. The thickness of the epithelium (hollow arrows in A and B) and the glandular proportion (a Reid index measure of the relative thickness of the glandular layer to the thickness of the entire wall consisting of mucosa and submucosa; solid arrows in A and B) were examined as an indication of inflammation. The measurements were focused on the olfactory epithelium from the dorsal meatus of the mouse nasal passages. (C) No significant differences were detected either in terms of the thickness of the epithelium (40.1 (24.2, 56.0) μm vs. 34.9 (20.6, 49.2) μm, t=0.77, p=0.47) or (D) the glandular proportion (51.5 (44.1, 58.9) % vs. 51.5 (45.1, 57.8) %, t=0.02, p=0.99), between CON and IN-DAN, respectively. The thickness was quantified as the average of three measurements in a randomly determined nasal section per mouse (N = 4 in each group). The unpaired t-test was used to analyze the data by GraphPad Prism 8.0. Data are presented as means with 95% CI. Scale bars: 50 μm (A and B).
See this image and copyright information in PMC

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