Ultrastructural Changes and Olfactory Deficits During 3-Methylindole-Induced Olfactory Mucosal Necrosis and Repair in Mice

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 7days. By 21 days, fibroblasts were less conspicuous, but Bowman's glands were rarely observed and were lined by epithelial cells withoutsecretory 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.