Selective damage to cochlear efferents by the choline neurotoxin ethylcholine mustard aziridinium ion (AF64A) in the chinchilla.
The cholinotoxin ethylcholine mustard aziridinium ion (AF64A) was diluted in artificial perilymph to concentrations ranging from 10-100 microM, injected unilaterally into the bulla of chinchillas, and allowed to passively diffuse across the round window membrane. Following 21-day survival, the animals were sacrificed and ears removed and embedded in epoxy for histological evaluation under both light and transmission electron microscopy. At 10 microM concentration, selective degeneration of efferent fibers was observed in the efferent terminals on outer hair cells (OHC), tunnel radial fibers, tunnel spiral bundle, and the inner spiral bundle. Serial sections of the middle turn of an animal at 10 microM concentrations showed normal efferent terminals on approximately 50% of OHCs. At the higher concentrations non-specific damage was seen in OHCs, afferents, and some supporting cells. These data suggest that low doses AF64A produces selective damage to cochlear efferent terminals and fibers in the chinchilla.
Smith
D W
DW
Department of Otolaryngology, University of Toronto, Canada.
Mount
R J
RJ
Callahan
J W
JW
D000818:Animals; D001388:Aziridines / Q000633:toxicity*; D002682:Chinchilla; D002794:Choline / Q000633:toxicity / Q000031:analogs & derivatives; D003051:Cochlea / Q000187:drug effects* / Q000294:innervation / Q000648:ultrastructure; D004525:Efferent Pathways / Q000187:drug effects / Q000648:ultrastructure; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity
D001388:Aziridines; D009498:Neurotoxins; C044894:ethylcholine aziridinium; D002794:Choline