Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / chemically induced*
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Alzheimer Disease / physiopathology
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Animals
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Arousal / drug effects
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Arousal / physiology
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Avoidance Learning / drug effects
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Avoidance Learning / physiology
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Azides / pharmacology*
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Discrimination Learning / drug effects
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Discrimination Learning / physiology
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Disease Models, Animal*
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Electron Transport Complex IV / antagonists & inhibitors*
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Electron Transport Complex IV / physiology
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Hippocampus / drug effects
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Hippocampus / physiopathology
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Male
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Mental Recall / drug effects
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Mental Recall / physiology
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Mitochondria / drug effects
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Mitochondria / physiology
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Motor Activity / drug effects
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Motor Activity / physiology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Orientation / drug effects
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Orientation / physiology
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Rats
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Rats, Inbred Strains
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Reaction Time / drug effects
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Reaction Time / physiology
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Retention, Psychology / drug effects
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Retention, Psychology / physiology
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Sodium Azide
Substances
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Azides
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Sodium Azide
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Electron Transport Complex IV