Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer's disease

J Alzheimers Dis. 2013;33(4):941-59. doi: 10.3233/JAD-2012-120397.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, accumulation of the amyloid-β peptide (Aβ), increase of oxidative stress, and synaptic alterations. The scavenging of reactive oxygen species through their matrix enzyme catalase is one of the most recognized functions of peroxisomes. The induction of peroxisome proliferation is attained through different mechanisms by a set of structurally diverse molecules called peroxisome proliferators. In the present work, a double transgenic mouse model of AD that co-expresses a mutant human amyloid-β protein precursor (AβPPswe) and presenilin 1 without exon 9 (PS1dE9) was utilized in order to assess the effect of peroxisomal proliferation on Aβ neurotoxicity in vivo. Mice were tested for spatial memory and their brains analyzed by cytochemical, electrophysiological, and biochemical methods. We report here that peroxisomal proliferation significantly reduces (i) memory impairment, found in this model of AD; (ii) Aβ burden and plaque-associated acetylcholinesterase activity; (iii) neuroinflammation, measured by the extent of astrogliosis and microgliosis; and (iv) the decrease in postsynaptic proteins, while promoting synaptic plasticity in the form of long-term potentiation. We concluded that peroxisomal proliferation reduces various AD neuropathological markers and peroxisome proliferators may be considered as potential therapeutic agents against the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Animals
  • Brain Chemistry / drug effects*
  • Brain Chemistry / genetics
  • Disease Models, Animal
  • Humans
  • Male
  • Memory Disorders / drug therapy*
  • Memory Disorders / genetics
  • Memory Disorders / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / genetics
  • Nerve Degeneration / pathology
  • Peroxisome Proliferators / administration & dosage*
  • Synapses / drug effects*
  • Synapses / pathology

Substances

  • Peroxisome Proliferators