Cytochrome oxidase inhibition: a novel animal model of Alzheimer's disease.
A profound decrease in activity of the mitochondrial enzyme cytochrome oxidase in blood platelets is a recently identified concomitant of Alzheimer's disease (AD). We investigated a possible pathogenic link between this finding and the symptoms of AD by mimicking this mitochondrial enzyme deficiency in rats. Rats were infused chronically with a selective inhibitor of cytochrome oxidase, sodium azide, or with saline delivered via subcutaneously implanted osmotic minipumps. The azide treatment impaired both spatial and nonspatial learning. Further, the azide treatment inhibited a low-threshold form of hippocampal long-term potentiation, primed burst potentiation. The behavioral deficits were not secondary to a sensory or motor impairment. Thus, chronic azide treatment of rats models some characteristics of AD.
Bennett
M C
MC
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Diamond
D M
DM
Stryker
S L
SL
Parks
J K
JK
Parker
W D
WD
D000544:Alzheimer Disease / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001386:Azides / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009949:Orientation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology; D019810:Sodium Azide
D001386:Azides; D019810:Sodium Azide; D003576:Electron Transport Complex IV