Reduction of hippocampal N-acetyl aspartate level in aged APP(Swe)/PS1(dE9) transgenic mice is associated with degeneration of CA3 pyramidal neurons

J Neurosci Res. 2010 Nov 1;88(14):3155-60. doi: 10.1002/jnr.22479.

Abstract

Age-related metabolic changes in the hippocampus of APP(Swe)/PS1(dE9) mice were measured with long echo-time in vivo (1)H-magnetic resonance spectroscopy ((1)H-MRS). Thioflavine S staining and Nissl staining were used to characterize deposition of Aβ aggregates and neuronal degeneration in the transgenic animals, respectively. The results showed that the APP(Swe)/PS1(dE9) mice had significantly decreased hippocampal N-acetyl aspartate (NAA)/total creatine (tCr) level at 16 months of age, which was associated with degeneration of and intracellular deposition of thioflavine S-positive materials in hippocampal CA3 pyramidal neurons. The results of this study provide direct evidence showing association among Aβ pathology (intracellular deposition of thioflavine S-positive materials), neuronal degeneration, and metabolic changes observable with in vivo (1)H-MRS in the hippocampus of APP(Swe)/PS1(dE9) mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Benzothiazoles
  • CA1 Region, Hippocampal / metabolism*
  • CA1 Region, Hippocampal / pathology
  • Creatine / metabolism
  • Disease Models, Animal
  • Down-Regulation / genetics*
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Presenilin-1 / genetics*
  • Presenilin-1 / metabolism
  • Pyramidal Cells / metabolism*
  • Pyramidal Cells / pathology
  • Pyramidal Cells / physiopathology
  • Thiazoles

Substances

  • Amyloid beta-Protein Precursor
  • Benzothiazoles
  • PSEN1 protein, human
  • Presenilin-1
  • Thiazoles
  • thioflavin T
  • Aspartic Acid
  • N-acetylaspartate
  • Creatine