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Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice

  1. R. Minkeviciene1,
  2. J. Ihalainen1,
  3. T. Malm1,
  4. O. Matilainen1,
  5. V. Keksa-Goldsteine1,
  6. G. Goldsteins1,
  7. H. Iivonen1,
  8. N. Leguit2,
  9. J. Glennon2,3,
  10. J. Koistinaho1,
  11. P. Banerjee4,
  12. H. Tanila1,5

Article first published online: 27 NOV 2007

DOI: 10.1111/j.1471-4159.2007.05147.x

Issue

Journal of Neurochemistry

Journal of Neurochemistry

Volume 105, Issue 3, pages 584–594, May 2008

Additional Information

How to Cite

Minkeviciene, R., Ihalainen, J., Malm, T., Matilainen, O., Keksa-Goldsteine, V., Goldsteins, G., Iivonen, H., Leguit, N., Glennon, J., Koistinaho, J., Banerjee, P. and Tanila, H. (2008), Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice. Journal of Neurochemistry, 105: 584–594. doi: 10.1111/j.1471-4159.2007.05147.x

Author Information

  1. 1

    A.I.Virtanen Institute for Molecular Sciences, University of Kuopio, Finland

  2. 2

    Solvay Pharmaceuticals Research Laboratories, Weesp, Netherlands

  3. 3

    Department of Chemistry, NUI Maynooth, Co. Kildare, Ireland

  4. 4

    Forest Laboratories, Jersey City, New Jersey, USA

  5. 5

    Department of Neurology, Kuopio University Hospital, Kuopio, Finland

*Address correspondence and reprint requests to Heikki Tanila, MD, PhD, Professor in Molecular Neurobiology, Department of Neurobiology, A. I. Virtanen Institute, University of Kuopio, P.O. Box 1627/ Neulaniementie 2, 70211 Kuopio, Finland. E-mail: Heikki.Tanila@uku.fi

Publication History

  1. Issue published online: 27 NOV 2007
  2. Article first published online: 27 NOV 2007
  3. Received October 23, 2007; revised manuscript received November 19, 2007; accepted November 20, 2007.

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Keywords:

  • Alzheimer’s disease;
  • cortex;
  • hippocampus;
  • microdialysis;
  • spatial memory

Abstract

We assessed baseline and KCl-stimulated glutamate release by using microdialysis in freely moving young adult (7 months) and middle-aged (17 months) transgenic mice carrying mutated human amyloid precursor protein and presenilin genes (APdE9 mice) and their wild-type littermates. In addition, we assessed the age-related development of amyloid pathology and spatial memory impaired in the water maze and changes in glutamate transporters. APdE9 mice showed gradual spatial memory impairment between 6 and 15 months of age. The stimulated glutamate release declined very robustly in 17-month-old APdE9 mice as compared to 7-month-old APdE9 mice. This age-dependent decrease in stimulated glutamate release was also evident in wild-type mice, although it was not as robust as in APdE9 mice. When compared to individual baselines, all aged wild-type mice showed 25% or greater increase in glutamate release upon KCl stimulation, but none of the aged APdE9 mice. There was an age-dependent decline in VGLUT1 levels, but not in the levels of VGLUT2, GLT-1 or synaptophysin. Astrocyte activation as measured by glial acidic fibrillary protein was increased in middle-aged APdE9 mice. Blunted pre-synaptic glutamate response may contribute to memory deficit in middle-aged APdE9 mice.

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