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

Nature Neuroscience volume 13, pages 411–413 (2010)Cite this article

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Abstract

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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Figure 1: Microglial CX3CR1-dependent neuron loss in 5xTg mice.

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Acknowledgements

We thank S. Oddo for generously providing the 3xTg-AD mice and P. Thevnaz and E. Meijering for the development of the ImageJ plugins stackreg and MTrackJ. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 596, A13), the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, 01GZ0713, 13N9268), the German Federal Ministry of Economics and Technology (Bundesministerium für Wirtschaft und Technologie, 16IN0675) and the European Union (Neuro.GSK3, FP-7-223276).

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Author notes

  1. Martin Fuhrmann and Tobias Bittner: These authors contributed equally to the work.

Authors and 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

Authors
  1. Martin Fuhrmann
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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.

Corresponding author

Correspondence to Jochen Herms.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5 and Supplementary Methods (PDF 4731 kb)

Supplementary Video 1

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. (MOV 3683 kb)

Supplementary Video 2

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. (MOV 1518 kb)

Supplementary Video 3

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. (MOV 1826 kb)

Supplementary Video 4

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. (MOV 1623 kb)

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Fuhrmann, M., Bittner, T., Jung, C. et al. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci 13, 411–413 (2010). https://doi.org/10.1038/nn.2511

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