Selective degeneration of a putative cholinergic pathway in the chinchilla cochlea following infusion with ethylcholine aziridinium ion.
Ethylcholine aziridinium ion (AF64A) diluted in artificial perilymph, or artificial perilymph alone was infused into the cochlea of chinchillas. After a survival time of 7 days, the cochleas were fixed with aldehydes, post-fixed in osmium and embedded in epoxy resin for light and electron microscopy. The ultrastructure of the cochleas infused with artificial perilymph was normal. Infusion of 1 microM AF64A resulted in massive degeneration of the axons of the lateral efferent system, a putative cholinergic pathway that originates in the brainstem and terminates on dendrites of the spiral ganglion innervating cochlear inner hair cells. The axons and terminals of a second putative cholinergic pathway, the medial efferent system which terminates on the outer hair cells, were normal. Infusion of AF64A in a concentration of 10 microM resulted in significant pathology of cochlear and supporting cells as well as the loss of efferent terminals at both inner and outer hair cell regions. The results suggest that AF64A is a selective neurotoxin when used under low-dosage conditions, and that certain pathways may be more susceptible to the effects of AF64A than others. One interpretation of these findings is that lateral efferent axons may have a higher rate of high-affinity choline uptake than terminals of the medial efferent axons.
Morley
B J
BJ
Research Division, Boys Town National Research Hospital, Omaha, NE 68131.
Spangler
K M
KM
Schneider
B L
BL
Javel
E
E
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D001388:Aziridines / Q000008:administration & dosage / Q000494:pharmacology*; D002682:Chinchilla; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects / Q000294:innervation*; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure; D007263:Infusions, Parenteral; D008854:Microscopy, Electron; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; C044894:ethylcholine aziridinium; D002794:Choline; D000109:Acetylcholine