Non-specific effects of the putative cholinergic neurotoxin ethylcholine mustard aziridinium ion in the rat brain examined by autoradiography, immunocytochemistry and gel electrophoresis.
Autoradiographic localisation of [3H]-ethylcholine mustard aziridinium ion (ECMA) after microinjection into the rat striatum has revealed intracellular sequestration of the toxin by glial and endothelial cells; fewer neuronal cells were labelled. Intrastriatal injection of 200 pmol ECMA caused severe cavitation of the tissue, extensive gliosis and permanent damage to myelinated structures, as revealed by immunocytochemical detection of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). These non-specific effects are in addition to ECMA's irreversible action on the choline carrier associated with cholinergic neurons, and only marginally protected by concomitant administration of the reversible choline transport inhibitor hemicholinium-3. They may instead be attributed to the powerful alkylating action that ECMA has on tissue proteins, as shown by fluorography of synaptosomal proteins treated with [3H]ECMA and separated by SDS-PAGE.
Allen
Y S
YS
MRC Brain, Behaviour and Psychiatry Group, Department of Neuropathology, Institute of Psychiatry, London, U.K.
Marchbanks
R M
RM
Sinden
J D
JD
D000818:Animals; D001345:Autoradiography; D001388:Aziridines / Q000493:pharmacokinetics / Q000633:toxicity*; D001389:Azirines / Q000633:toxicity*; D002794:Choline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009498:Neurotoxins / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001388:Aziridines; D001389:Azirines; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D009498:Neurotoxins; C044894:ethylcholine aziridinium; D002794:Choline