Cytochrome oxidase inhibition: a novel animal model of Alzheimer's disease

J Geriatr Psychiatry Neurol. Apr-Jun 1992;5(2):93-101. doi: 10.1177/002383099200500206.

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

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / physiopathology
  • Animals
  • Arousal / drug effects
  • Arousal / physiology
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Azides / pharmacology*
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology
  • Disease Models, Animal*
  • Electron Transport Complex IV / antagonists & inhibitors*
  • Electron Transport Complex IV / physiology
  • Hippocampus / drug effects
  • Hippocampus / physiopathology
  • Male
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Orientation / drug effects
  • Orientation / physiology
  • Rats
  • Rats, Inbred Strains
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Retention, Psychology / drug effects
  • Retention, Psychology / physiology
  • Sodium Azide

Substances

  • Azides
  • Sodium Azide
  • Electron Transport Complex IV