Effects of the cholinotoxin, AF64A, on neuronal trace-metal distribution in the rat hippocampus and neocortex.
Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxin which is specific for cholinergic nerve terminals. Besides its effects on elements of the acetylcholine system, we observed that, after 2 and 8 days, a single 20-nmol intracerebroventricular dose altered the Timm's staining of certain regions of the central nervous system and reduced the tissue levels of trace metals. In the hippocampal formation, there was a considerable decrease in the staining of the neuropil of the stratum radiatum and stratum oriens, which contain cholinergic nerve terminals. A reduction in staining was also demonstrated in the perikarya of cortical pyramidal cells. The diminished trace-metal level in both regions was confirmed by quantitative measurements of zinc and copper levels. A similar reduction was not observed at a lower dose (8 nmol) of the cholinotoxin. The results led to the conclusion that AF64A may cause the decrease of the trace-metal content of the postsynaptic neurons through an indirect mechanism.
D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014131:Trace Elements / Q000032:analysis*; D015032:Zinc / Q000378:metabolism*
D001388:Aziridines; D001389:Azirines; D009466:Neuromuscular Blocking Agents; D014131:Trace Elements; D003300:Copper; C044894:ethylcholine aziridinium; D015032:Zinc; D002794:Choline