Reversible cholinergic changes induced by AF64A in rat hippocampus and possible septal compensatory effect.
Ethylcholine aziridinium (AF64A) was injected intracerebroventricularly in rats, and the dose- and time-dependent effect of this treatment was measured on cholinergic markers in different areas of the brain. Choline acetyltransferase (ChAT) in the hippocampus was reduced by 0, 25, 40 and 50%, 4 days after administration of 0.25, 0.5, 1.0 and 2.0 nmol/side of AF64A. This effect was paralleled by a 0, 21, 38 and 48% increase in septal ChAT, at the same time and dose, respectively. Hippocampal and septal ChAT returned to normal by 14 days, following the two smaller doses of AF64A. Normal values of ChAT activity in the hippocampus were measured by 3 months post-1.0 nmol/side and by 12 months after 2.0 nmol AF64A/side. A transient secondary increase in septal ChAT was measured at 28 and 42 days after 1.0 nmol/side, after which no further changes were measured in this area. High affinity choline transport (HAChT) in the hippocampus showed a 35 and 25% decrease but only 14 and 7 days, after injection of 0.25 and 0.5 nmol AF64A/side, respectively. However, significant reductions by 45% at 14 days and by 65% at 4 days, were measured after the infusion of 1.0 and 2.0 nmol/side, respectively. This effect was significantly attenuated by 3 months and returned to normal by 12 months after treatment. Acetylcholinesterase (AChE) activity in the hippocampus was most severely affected by AF64A. Specifically, significant inhibition of 20% (by 7 days), 35% (by 7 days), 25% (by 2 days) and 30% (by 2 days) was observed at 0.25, 0.5, 1.0 and 2.0 nmol AF64A/side, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
el Tamer
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Loyola University Chicago, Stritch School of Medicine, Department of Pharmacology and Experimental Therapeutics, Maywood, IL 60153.
Corey
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J
Wülfert
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E
Hanin
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D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001388:Aziridines / Q000008:administration & dosage / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors
D001388:Aziridines; D009498:Neurotoxins; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline; D000109:Acetylcholine