Cholinotoxicity induced by ethylcholine aziridinium ion after intracarotid and intracerebroventricular administration.
The effect of ethylcholine aziridinium ion (AF64A) after an intracerebroventricular (icv) injection was compared to that obtained after an intravascular administration. Reductions in choline acetyltransferase (ChAT) and acetylcholinesterase activities in the hippocampus but not in the cerebral cortex or the corpus striatum were observed 10 days after bilateral injection of AF64A into the rat cerebroventricles (3 nmol/side). However, when AF64A was injected into the carotid artery (1 mumol/kg) following a unilateral opening of the blood-brain barrier by a hypertonic treatment, a significant decrease in ChAT activity was observed in the ipsilateral side of the cerebral cortex but not in hippocampus, corpus striatum, or cerebellum. High-affinity choline transport was reduced significantly 11 days after an icv injection of AF64A in all the above mentioned brain regions, and recovered 60 days post injection in the cerebral cortex and in the corpus striatum but not in the hippocampus. Our results suggest that in various brain regions, AF64A causes various degrees of damage to cholinergic neurons, depending on the quantity of the toxin that reaches the target tissue.
Pittel
Z
Z
Israel Institute for Biological Research, Ness-Ziona.
Fisher
A
A
Heldman
E
E
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001388:Aziridines / Q000008:administration & dosage / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D001692:Biological Transport; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002339:Carotid Arteries; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007269:Injections, Intra-Arterial; D007276:Injections, Intraventricular; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism
D001388:Aziridines; D001389:Azirines; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline