Altered neurochemical profile in the McGill-R-Thy1-APP rat model of Alzheimer's disease: a longitudinal in vivo 1H MRS study

Authors

  • Linn H. Nilsen,

    1. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
    Search for more papers by this author
  • Torun M. Melø,

    1. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
    Search for more papers by this author
  • Oddbjørn Sæther,

    1. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
    Search for more papers by this author
  • Menno P. Witter,

    1. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
    2. Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory, Norwegian University of Science and Technology, Trondheim, Norway
    Search for more papers by this author
  • Ursula Sonnewald

    Corresponding author
    1. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
    • Address correspondence and reprint requests to Ursula Sonnewald, Faculty of Medicine, Department of Neuroscience, PO box 8905, MTFS, 7491 Trondheim, Norway. E-mail: Ursula.sonnewald@ntnu.no

    Search for more papers by this author

Abstract

We investigated metabolite levels during the progression of pathology in McGill-R-Thy1-APP rats, a transgenic animal model of Alzheimer's disease, and in healthy age-matched controls. Rats were subjected to in vivo 1H magnetic resonance spectroscopy (MRS) of the dorsal hippocampus at age 3, 9 and 12 months and of frontal cortex at 9 and 12 months. At 3 months, a stage in which only Aβ oligomers are present, lower glutamate, myo-inositol and total choline content were apparent in McGill-R-Thy1-APP rats. At age 9 months, lower levels of glutamate, GABA, N-acetylaspartate and total choline and elevated myo-inositol and taurine were found in dorsal hippocampus, whereas lower levels of glutamate, GABA, glutamine and N-acetylaspartate were found in frontal cortex. At age 12 months, only the taurine level was significantly different in dorsal hippocampus, whereas taurine, myo-inositol, N-acetylaspartate and total creatine levels were significantly higher in frontal cortex. McGill-R-Thy1-APP rats did not show the same changes in metabolite levels with age as displayed in the controls, and overall, prominent and complex metabolite differences were evident in this transgenic rat model of Alzheimer's disease. The findings also demonstrate that in vivo 1H MRS is a powerful tool to investigate disease-related metabolite changes in the brain.

Ancillary