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ResearchIn-Press PreviewCell biologyNeuroscience Open Access | 10.1172/JCI200121

Disruption of CSF-1 receptor-mediated metal ion homeostasis in the murine brain promotes neurodegenerative disease

Violeta Chitu,1 Julia Alvarenga,1 Wenna Chen,2 David Reynolds,2 Yang Liu,2 Daqian Sun,3 Anders Sandell,4 Virginjia Danylaite Karrenbauer,5 Per Uvdal,6 Iran A.N. da Silva,7 Christophe Sandt,8 Oxana Klementieva,7 Ulf Johansson,9 Kavitha Subramanian Vignesh,10 Zbigniew K. Wszolek,11 Dennis W. Dickson,12 Jennifer Aguilan,13 Simone Sidoli,14 Deyou Zheng,2 and E. Richard Stanley1

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Chitu, V. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Alvarenga, J. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Chen, W. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Reynolds, D. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Liu, Y. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Sun, D. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

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1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Danylaite Karrenbauer, V. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

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1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by da Silva, I. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Sandt, C. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

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1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Johansson, U. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Subramanian Vignesh, K. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

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1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

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1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

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1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Sidoli, S. in: PubMed | Google Scholar

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

Find articles by Zheng, D. in: PubMed | Google Scholar |

1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States of America

2Department of Genetics, Albert Einstein College of Medicine, New York, United States of America

3Department of Cell Biology, Albert Einstein College of Medicine, New York, United States of America

4Division of X-ray Photon Science, Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden

5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

6Chemical Physics, Department of Chemistry, Lund University, Lund, Sweden

7NanoLund, Lund University, Lund, Sweden

8Synchrotron SOLEIL, Saint-Aubin, France

9MAX IV Laboratory, Lund University, Lund, Sweden

10Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, United States of America

11Department of Neurology, Mayo Clinic, Jacksonville, United States of America

12Department of Neuroscience, Mayo Clinic, Jacksonville, United States of America

13Department of Pathology, Albert Einstein College of Medicine, New York, United States of America

14Department of Biochemistry, Albert Einstein College of Medicine, New York, United States of America

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Published February 26, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI200121.
Copyright © 2026, Chitu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 26, 2026 - Version history
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Abstract

Dominant-inactivating mutations in the colony stimulating factor-1 receptor (CSF1R) cause CSF-1R related leukoencephalopathy (CRL), an adult-onset neurodegenerative disease that is modeled in the Csf1r+/– mouse. CRL is caused by microglial dysfunction. However, the primary microglial deficit, is unknown. To address this question, we employed single-nucleus RNA sequencing of brains from young Csf1r+/– mice without pathological or behavioral alterations. Reduction of CSF-1R signaling caused metal ion accumulation in brain macrophages, with concomitant activation of cell death and stress response pathways in oligodendrocytes and neuronal subpopulations. Reduction of metallothionein 1 (Mt1) and 3 (Mt3) gene expression was a common feature in glial and neuronal cells of Csf1r+/– mice. Overexpression of Mt1 restored metal ion homeostasis, normalized ROS production in microglia, and prevented the development of behavioral deficits, while Mt3 deletion had disease-enhancing effects. These findings demonstrate CSF-1R regulation of metal ion homeostasis via metallothioneins in the brain.

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