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The subpopulation of microglia expressing functional muscarinic acetylcholine receptors expands in stroke and Alzheimer’s disease

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Abstract

Microglia undergo a process of activation in pathology which is controlled by many factors including neurotransmitters. We found that a subpopulation (11 %) of freshly isolated adult microglia respond to the muscarinic acetylcholine receptor agonist carbachol with a Ca2+ increase and a subpopulation of similar size (16 %) was observed by FACS analysis using an antibody against the M3 receptor subtype. The carbachol-sensitive population increased in microglia/brain macrophages isolated from tissue of mouse models for stroke (60 %) and Alzheimer’s disease (25 %), but not for glioma and multiple sclerosis. Microglia cultured from adult and neonatal brain contained a carbachol-sensitive subpopulation (8 and 9 %), which was increased by treatment with interferon-γ to around 60 %. This increase was sensitive to blockers of protein synthesis and correlated with an upregulation of the M3 receptor subtype and with an increased expression of MHC-I and MHC-II. Carbachol was a chemoattractant for microglia and decreased their phagocytic activity.

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Acknowledgments

This project was funded by Deutsche Forschungsgemeinschaft (SFB-TRR43) and Neurocure. We would like to thank Frank Heppner, Stefan Prokop and Mathias Jucker for providing the APPPS1 mice. We would also like to thank Regina Piske and Irene Haupt for excellent technical assistance. Vincent Prinz is a participant in the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13125, Berlin, Germany

    Maria Pannell, Maria Almut Meier, Frank Szulzewsky, Vitali Matyash, Susanne A. Wolf & Helmut Kettenmann

  2. Department of Neurology, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany

    Matthias Endres, Golo Kronenberg & Vincent Prinz

  3. Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13125, Berlin, Germany

    Sonia Waiczies

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  1. Maria Pannell
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  2. Maria Almut Meier
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Correspondence to Helmut Kettenmann.

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S. A. Wolf and H. Kettenmann contributed equally as last authors.

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Pannell, M., Meier, M.A., Szulzewsky, F. et al. The subpopulation of microglia expressing functional muscarinic acetylcholine receptors expands in stroke and Alzheimer’s disease. Brain Struct Funct 221, 1157–1172 (2016). https://doi.org/10.1007/s00429-014-0962-y

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  • DOI: https://doi.org/10.1007/s00429-014-0962-y

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