Damage to cochlear efferents following AF64A intoxication.
Damage to cochlear efferents in chinchillas was assessed using transmission electron microscopy following unilateral treatment with the cholinotoxin ethylcholine mustard aziridinium ion (AF64A). AF64A was diluted in artificial perilymph to concentrations ranging from 0.5 to 100 microM. Survival times ranged from 1 to 12 weeks. At concentrations above 10 microM, widespread damage was noted to efferent fibers within the inner spiral bundle (ISB), tunnel spiral bundle (TSB), tunnel radial fibers (TRF) and efferent terminals at the base of OHCs. This damage included degeneration of fibers and terminals, delamination of mitochondria, vacuolization, and loss of cell membrane. However, at high concentrations, non-specific damage was also noted as thinnings or discontinuities of the membrane of OHCs and afferent fibers. At concentrations between 3 and 10 microM, selective damage was observed to efferent fibers within the ISB, TSB, TRF, and to terminals at the base of the OHCs, with all other structures appearing normal. At concentrations of 0.5 and 1 microM, damage was limited to efferent fibers within the TSB and ISB below the inner hair cells. In general, insult was greatest to middle- and basal-turn efferents, and longer survival times did not produce greater damage to, or loss of, efferents. These data suggest that at low concentrations, AF64A produces a partial yet selective degeneration of cochlear efferents within both the medial and lateral tracts, and that at the lowest concentrations used in these studies, AF64A produces a preferential insult on lateral olivocochlear efferents.
Department of Otolaryngology, University of Toronto Faculty of Medicine, Ontario, Canada.
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D000818:Animals; D001388:Aziridines / Q000008:administration & dosage / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival; D002682:Chinchilla; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D003051:Cochlea / Q000187:drug effects / Q000294:innervation* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009410:Nerve Degeneration; D009411:Nerve Endings / Q000187:drug effects / Q000473:pathology; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D009476:Neurons, Efferent / Q000187:drug effects* / Q000473:pathology; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000473:pathology; D014118:Toxins, Biological / Q000008:administration & dosage / Q000633:toxicity*; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D001388:Aziridines; D014118:Toxins, Biological; C044894:ethylcholine aziridinium; D002794:Choline