IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms13441.html
   My bibliography  Save this article

Mapping synaptic glutamate transporter dysfunction in vivo to regions surrounding Aβ plaques by iGluSnFR two-photon imaging

Author

Listed:
  • J. K. Hefendehl

    (Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia)

  • J. LeDue

    (Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia)

  • R. W. Y. Ko

    (Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia)

  • J. Mahler

    (Hertie-Institut für klinische Hirnforschung)

  • T. H. Murphy

    (Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia)

  • B. A. MacVicar

    (Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia)

Abstract

Amyloid-β (Aβ) plaques, a hallmark of Alzheimer’s disease (AD), are surrounded by regions of neuronal and glial hyperactivity. We use in vivo two-photon and wide-field imaging of the glutamate sensor iGluSnFR to determine whether pathological changes in glutamate dynamics in the immediate vicinity of Aβ deposits in APPPS1 transgenic mice could alter neuronal activity in this microenvironment. In regions close to Aβ plaques chronic states of high spontaneous glutamate fluctuations are observed and the timing of glutamate responses evoked by sensory stimulation exhibit slower decay rates in two cortical brain areas. GLT-1 expression is reduced around Aβ plaques and upregulation of GLT-1 expression and activity by ceftriaxone partially restores glutamate dynamics to values in control regions. We conclude that the toxic microenvironment surrounding Aβ plaques results, at least partially, from enhanced glutamate levels and that pharmacologically increasing GLT-1 expression and activity may be a new target for early therapeutic intervention.

Suggested Citation

  • J. K. Hefendehl & J. LeDue & R. W. Y. Ko & J. Mahler & T. H. Murphy & B. A. MacVicar, 2016. "Mapping synaptic glutamate transporter dysfunction in vivo to regions surrounding Aβ plaques by iGluSnFR two-photon imaging," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13441
    DOI: 10.1038/ncomms13441
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13441
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13441?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13441. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.