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Local self-renewal can sustain CNS microglia maintenance and function throughout adult life

Nature Neuroscience volume 10, pages 1538–1543 (2007)Cite this article

Abstract

Microgliosis is a common response to multiple types of damage in the CNS. However, the origin of the cells involved in this process is still controversial and the relative importance of local expansion versus recruitment of microglia progenitors from the bloodstream is unclear. Here, we investigated the origin of microglia using chimeric animals obtained by parabiosis. We found no evidence of microglia progenitor recruitment from the circulation in denervation or CNS neurodegenerative disease, suggesting that maintenance and local expansion of microglia are solely dependent on the self-renewal of CNS resident cells in these models.

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Figure 1: Blood chimerism in parabiotic and lethally irradiated/transplanted mice.
Figure 2: Circulating progenitors do not contribute to the microgliosis that is induced by facial nerve axotomy in parabiotic mice.
Figure 3: Circulating progenitors do not contribute to the microgliosis induced by ALS in the spinal cord of parabiotic mSOD transgenic mice.
Figure 4: Irradiation is not sufficient to trigger the entry of blood born microglia progenitors into the CNS.

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Acknowledgements

We thank S.Y. Corbel, L. So, C.K. Lam and L. Yi for expert assistance, B. Chua, K. Ranta and the BRC animal unit personnel for advice on animal welfare, and K.M. McNagny for critical evaluation of the manuscript. This work was supported by Canadian Institute for Health Research (CIHR) grants to F.M.V.R. (MOP 81382) and to W.T. (MOP 42480), a Neuromuscular Research Partnership grant from CIHR, a ALS Society of Canada and Muscular Dystrophy Canada grant to C.K. and F.M.V.R. (JNM-69682) and a Collaborative Health Research Grant from CIHR and Natural Science and Engineering Research Council to C.K. and F.M.V.R. (CHRP 299119). J.L.B. is supported by a Multiple Sclerosis Society of Canada Postdoctoral Research Fellowship.

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Authors and Affiliations

  1. University of British Columbia, The Biomedical Research Centre, 2222 Health Sciences Mall, Vancouver, V6T 1Z3, British Columbia, Canada

    Bahareh Ajami, Jami L Bennett, Charles Krieger, Wolfram Tetzlaff & Fabio M V Rossi

  2. School of Kinesiology, Simon Fraser University, Burnaby, V5A 1S6, British Columbia, Canada

    Charles Krieger

  3. Division of Neurology, Department of Medicine, Neuromuscular Disease Unit, HHSC, Vancouver, V5Z 1M9, British Columbia, Canada

    Charles Krieger

  4. International Collaboration On Repair Discoveries and Departments of Zoology and Surgery, University of British Columbia, Vancouver, V6T 1Z4, British Columbia, Canada

    Wolfram Tetzlaff

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  1. Bahareh Ajami
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  2. Jami L Bennett
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Contributions

B.A. conducted all of the experiments and participated in experimental design and interpretation as well as in the writing of the manuscript. J.L.B. provided guidance in designing and conducting the flow cytometry and participated in writing the manuscript. C.K. participated in writing the manuscript and designing the ALS experiments. W.T. conducted the facial axotomy surgeries and participated in the design of experiments as well as in the writing of the manuscript. F.M.V.R. designed and interpreted experiments, and wrote the manuscript.

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Correspondence to Fabio M V Rossi.

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Ajami, B., Bennett, J., Krieger, C. et al. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10, 1538–1543 (2007). https://doi.org/10.1038/nn2014

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