AF64A-induced brain damage and its relation to dementia.
Several data obtained in the AF64A-model are of particular relevance for our understanding of the pathogenesis and progression of Alzheimer's disease. The AF64A-induced withdrawal of cholinergic function in the rat hippocampus was associated with reversible functional changes in other neurotransmitters, including noradrenaline, serotonin, somatostatin and glutamate, thereby mimicking changes in Alzheimer's disease. Identical changes in markers for synaptic vesicles were found in Alzheimer's disease and AF64A-model. A study on the role of gender revealed a higher susceptibility to the neurotoxic action of AF64A in female rats. The cholinergic deficit was also responsible for a disinhibition of the negative feedback regulation of glucocorticoids. Increased exposure to glucocorticoids, however, enhanced the vulnerability of hippocampal cholinergic neurons to AF64A. These data indicate that the AF64A-induced cholinergic deficit in the rat brain represents a reliable tool to study several mechanisms possibly involved in Alzheimer's disease.
Hörtnagl
H
H
Institute of Biochemical Pharmacology, University of Vienna, Austria.
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001388:Aziridines / Q000633:toxicity*; D001925:Brain Damage, Chronic / Q000139:chemically induced / Q000378:metabolism*; D002794:Choline / Q000031:analogs & derivatives* / Q000633:toxicity; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology; D005246:Feedback; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000633:toxicity; D009498:Neurotoxins / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012727:Sex Characteristics; D013004:Somatostatin / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism
D001388:Aziridines; D005938:Glucocorticoids; D009466:Neuromuscular Blocking Agents; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D012701:Serotonin; D018698:Glutamic Acid; D013004:Somatostatin; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine; D003345:Corticosterone; D009638:Norepinephrine