Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease

Curr Alzheimer Res. 2013 May 1;10(4):406-19. doi: 10.2174/1567205011310040006.


This study aimed to show that the rat model of sporadic Alzheimer's disease (sAD) generated by the intracerebroventricular (icv) injection of a sub-diabetogenic dose of streptozotocin (icvSTZ) is characterized by brain mitochondrial abnormalities. Three-month-old male Wistar rats were investigated 5 weeks after a single bilateral icv injection of STZ (3 mg/ Kg) or vehicle. icvSTZ administration induced a decrease in brain weight and cognitive decline, without affecting blood glucose levels. icvSTZ administration also resulted in a significant increase in hippocampal amyloid beta peptide 1-42 (Aβ(1-42)) levels as well as in cortical and hippocampal hyperphosphorylated tau protein levels. Brain mitochondria from icvSTZ rats revealed deficits in their function, as shown by a decrease in mitochondrial transmembrane potential, repolarization level, ATP content, respiratory state 3, respiratory control ratio and ADP/O index and an increase in lag phase of repolarization. Mitochondria from icvSTZ rats also displayed a decrease in pyruvate and α-ketoglutarate dehydrogenases and cytochrome c oxidase activities and an increase in the susceptibility to calcium-induced mitochondrial permeability transition. An increase in hydrogen peroxide and lipid peroxidation levels and a reduction in glutathione content were also observed in mitochondria from icvSTZ rats. These results demonstrate that the insulin-resistant brain state that characterizes this rat model of sAD is accompanied by the occurrence of mitochondrial abnormalities reinforcing the validity of this animal model to study sAD pathogenesis and potential therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / metabolism
  • Alzheimer Disease / blood
  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Blood Glucose
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain / ultrastructure*
  • Disease Models, Animal
  • Escape Reaction / drug effects
  • Glutathione
  • Glutathione Disulfide / metabolism
  • Hydrogen Peroxide / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Microscopy, Electron, Transmission
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Oxygen Consumption
  • Rats
  • Rats, Wistar
  • Reaction Time
  • Streptozocin / toxicity*


  • Adenine Nucleotides
  • Amyloid beta-Peptides
  • Antibiotics, Antineoplastic
  • Blood Glucose
  • Malondialdehyde
  • Streptozocin
  • Hydrogen Peroxide
  • Glutathione
  • Glutathione Disulfide