Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease

Journal name:
Nature Neuroscience
Volume:
13,
Pages:
411–413
Year published:
DOI:
doi:10.1038/nn.2511
Received
Accepted
Published online

Microglia, the immune cells of the brain, can have a beneficial effect in Alzheimer's disease by phagocytosing amyloid-β. Two-photon in vivo imaging of neuron loss in the intact brain of living Alzheimer's disease mice revealed an involvement of microglia in neuron elimination, indicated by locally increased number and migration velocity of microglia around lost neurons. Knockout of the microglial chemokine receptor Cx3cr1, which is critical in neuron-microglia communication, prevented neuron loss.

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Author information

  1. These authors contributed equally to the work.

    • Martin Fuhrmann &
    • Tobias Bittner

Affiliations

  1. Center of Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.

    • Martin Fuhrmann,
    • Tobias Bittner,
    • Christian K E Jung,
    • Steffen Burgold,
    • Gerda Mitteregger,
    • Hans Kretzschmar &
    • Jochen Herms
  2. German Center for Neurodegenerative Diseases Munich, Ludwig-Maximilians-University, Munich, Germany.

    • Richard M Page &
    • Christian Haass
  3. Department of Neurobiology and Behavior, University of California, Irvine, California, USA.

    • Frank M LaFerla

Contributions

M.F. and T.B. conducted the experiments and wrote the manuscript. C.K.E.J. and S.B. provided technical assistance. R.M.P. performed Aβ measurements. G.M., H.K., C.H. and F.M.L. provided mouse models and helpful discussion. J.H. coordinated the research and supervised the project.

Competing financial interests

The authors declare no competing financial interests.

Corresponding author

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Supplementary information

PDF files

  1. Supplementary Text and Figures (5M)

    Supplementary Figures 1–5 and Supplementary Methods

Movies

  1. Supplementary Video 1 (4M)

    Example of a z stack acquired by two-photon in vivo imaging. Z stack from 650 μm depth to the surface in a living mouse brain. Neurons are labeled with YFP and microglia with GFP.

  2. Supplementary Video 2 (2M)

    Tracking of microglia migration in vivo. 5-week time-lapse example of microglia migration around a neuron. Colored lines representing the tracks of the microglia are superimposed.

  3. Supplementary Video 3 (2M)

    Screening behavior of microglia with extension and retraction of fine processes. The video consists of z stack projections (40 μm) of fluorescence images recorded with a time interval of 5 min 150 μm below the brain surface.

  4. Supplementary Video 4 (2M)

    Turnover rate (TOR) of microglia. Red/green overlay of subsequent time points to visualize gained (green) and lost (red) as well as stable (yellow) areas of microglial processes.

Additional data