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Ultrastructural changes and olfactory deficits during 3-methylindole-induced olfactory mucosal necrosis and repair in
Margaret A Miller1, Melissa A O'Bryan
1Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, UMC Veterinary Medfical Diagnostic Laboratory, PO Box 6023, Columbia, MO 65205, USA. millerma@missouri.edu
Abstract:
Olfactory mucosa from C57BL/6N mice was examined by transmission electron microscopy at 0.5, 1, 2, 4, 6, 24, 48, and 72 h after 400 mg 3-methylindole (3MI)/kg ip, and at 7, 14, and 21 days after 300 mg 3MI/kg or vehicle. Degeneration was evident in epithelial cells of Bowman's glands and olfactory sustentacular cells by 0.5 h, but not in neurons until 24 h, by which time necrosis was fully developed in sustentacular cells and epithelium of Bowman's glands. Sustentacular cells and neurons detached from the basal lamina by 48 h. Lamina proprial fibroblasts were hypertrophied by 72 h and, with collagen fibrils, formed the bulk of the mucosa at 7 days. By 21 days, fibroblasts were less conspicuous, but Bowman's glands were rarely observed and were lined by epithelial cells without secretory granules. Mucosal epithelium was reconstituted, but disorderly and lacked olfactory differentiation. Mice treated with 3MI were more likely than control mice to taste water treated with isoamyl acetate (odorant) and quinine monohydrochloride (aversive tastant). Though olfactory neurons were initially spared, their absence in the regenerated epithelium explains lingering olfactory deficits in murine 3MI toxicosis.
Insights
3-methylindole (3MI) causes olfactory mucosa damage, initially sparing neurons but leading to lasting olfactory deficits due to disorganized regeneration. This study details the cellular timeline of 3MI toxicosis in mice.
Area of Science:
- Toxicology
- Neuroscience
- Cell Biology
Background:
- 3-methylindole (3MI) is a known toxicant affecting the olfactory system.
- Understanding the temporal progression of 3MI-induced damage is crucial for developing interventions.
Purpose of the Study:
- To investigate the time-dependent effects of 3-methylindole (3MI) on the murine olfactory mucosa.
- To characterize the cellular mechanisms underlying olfactory deficits following 3MI exposure.
Main Methods:
- Transmission electron microscopy was used to examine olfactory mucosa from C57BL/6N mice.
- Mice were administered 3MI at different doses and time points (0.5 h to 21 days).
Main Results:
- Early degeneration observed in Bowman's gland epithelium and sustentacular cells (by 0.5 h), with neuronal damage evident later (by 24 h).
- Sustentacular cells and neurons detached by 48 h; fibroblasts proliferated by 72 h, forming the mucosal bulk by 7 days.
- By 21 days, olfactory epithelium regenerated but lacked olfactory differentiation, correlating with impaired odorant detection.
Conclusions:
- 3MI causes progressive damage to the olfactory mucosa, with initial sparing of olfactory neurons followed by their eventual loss.
- Disorganized regeneration of the olfactory epithelium underlies persistent olfactory dysfunction in 3MI toxicosis.
- The study provides a detailed cellular timeline of 3MI-induced olfactory toxicity.