Ultrastructural and neurochemical effects of the presumed cholinergic toxin AF64A in the rat interpeduncular nucleus.
We have studied the effect of the presumptive cholinergic neurotoxin, ethylcholine mustard aziridinium ion (compound AF64A), on ultrastructure and neurochemical markers in the rat interpeduncular nucleus (IPN). Stereotaxic injections of 1 nmol of AF64A resulted in extensive degeneration of synaptic terminals within 40 h. Ultrastructural damage to neuronal cell bodies, dendrites and axons was also sometimes observed at this stage. Five days after the injection, more severe degenerative changes were observed in a larger number of neuronal cell bodies, axons and dendrites. High affinity uptake of [3H]choline, but not [3H]GABA, was significantly decreased 24 h after toxin injection. Five days after the injection, not only choline acetyltransferase but also glutamate decarboxylase levels were significantly decreased. Our results suggest that, in addition to presynaptic cholinergic neurotoxicity, AF64A also leads to degenerative alterations of non-cholinergic neurons. Our electron microscopic observations constitute the first ultrastructural report on neuropathological damage caused by AF64A.
D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001388:Aziridines; D001389:Azirines; D005680:gamma-Aminobutyric Acid; C044894:ethylcholine aziridinium; D002794:Choline