Ethylcholine mustard aziridinium ion lesions of the rat cortex result in retrograde degeneration of basal forebrain cholinergic neurons: implications for animal models of neurodegenerative disease.
Multiple injections of 2 nmols of cyclised ethylcholine mustard aziridinium ion (ECMA), a putative cholinergic neurotoxin, were made (unilaterally) into the cortical terminal field of cholinergic neurons projecting from the nucleus basalis of Meynert (NBM) in the rat basal forebrain. After 30 days, choline acetyltransferase enzymatic activity, a marker for cholinergic function, was significantly lowered in both ipsilateral cortex and NBM, and cholinergic cell bodies in the latter reduced in cross-sectional area, a spectrum of effects characteristic of retrograde degeneration of this pathway. These results are discussed in the context of neurodegenerative diseases affecting cholinergic function.
D000544:Alzheimer Disease / Q000139:chemically induced*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*; D012183:Retrograde Degeneration / Q000187:drug effects*; D013377:Substantia Innominata / Q000187:drug effects*
D001388:Aziridines; D001389:Azirines; D011950:Receptors, Cholinergic; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline