Decreased microglial Wnt/β-catenin signalling drives microglial pro-inflammatory activation in the developing brain

Author:

Van Steenwinckel Juliette12ORCID,Schang Anne-Laure123,Krishnan Michelle L4,Degos Vincent125,Delahaye-Duriez Andrée16,Bokobza Cindy12,Csaba Zsolt12,Verdonk Franck78,Montané Amélie12,Sigaut Stéphanie12,Hennebert Olivier129,Lebon Sophie12,Schwendimann Leslie12,Le Charpentier Tifenn12,Hassan-Abdi Rahma12,Ball Gareth4ORCID,Aljabar Paul4,Saxena Alka10,Holloway Rebecca K11,Birchmeier Walter12,Baud Olivier12,Rowitch David13,Miron Veronique11,Chretien Fabrice6714,Leconte Claire15ORCID,Besson Valérie C15,Petretto Enrico G16,Edwards A David4,Hagberg Henrik417,Soussi-Yanicostas Nadia12,Fleiss Bobbi12418,Gressens Pierre124

Affiliation:

1. Université de Paris, NeuroDiderot, Inserm, F-75019 Paris, France

2. PremUP, F-75006 Paris, France

3. UMR CNRS 8638-Chimie Toxicologie Analytique et Cellulaire, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, 4 Avenue de l'Observatoire, F-75006 Paris, France

4. Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London, SE1 7EH, UK

5. Department of Anesthesia and Intensive Care, Pitié Salpétrière Hospital, F-75013 Paris France

6. UFR de Santé, Médecine et Biologie Humaine, Université Paris 13, Sorbonne Paris Cité, F-93000 Bobigny, France

7. Infection and Epidemiology Department, Human Histopathology and Animal Models Unit, Institut Pasteur, F-75015 Paris, France

8. Paris Descartes University, Sorbonne Paris Cité, F-75006 Paris, France

9. Conservatoire national des arts et métiers, F-75003 Paris, France

10. Genomics Core Facility, NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, SE1 9RT, UK

11. MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, UK

12. Cancer Research Program, Max Delbrueck Center for Molecular Medicine in the Helmholtz Society, Berlin-Buch, Germany

13. Department of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UK

14. Laboratoire de Neuropathologie, Centre Hospitalier Sainte Anne, F-75014 Paris, France

15. EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, F-75006 Paris, France

16. Duke-NUS Medical School, 8 College Road 169857, Singapore

17. Perinatal Center, Institute of Clinical Sciences and Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, 41390 Gothenburg, Sweden

18. School of Health and Biomedical Sciences, RMIT University, Bundoora, 3083, VIC, Australia

Abstract

Inflammatory activation of microglia in the brains of prematurely born infants can lead to permanent neurological sequelae. Van Steenwinckel et al. show that a reduction in microglial Wnt signalling is necessary and sufficient to drive a microglial phenotype causing hypomyelination, and establish the Wnt pathway as a viable therapeutic target.

Funder

Université Paris Diderot

Université Sorbonne-Paris-Cité, Investissement d'Avenir

ERA-NET Neuron

Association Robert Debré, PremUP, Fondation de France

Fondation pour la Recherche sur le Cerveau

Fondation des Gueules Cassées, Roger de Spoelberch Foundation, Grace de Monaco Foundation

Leducq Foundation, Action Medical Research

Cerebral Palsy Alliance Research Foundation Australia

Wellcome Trust

Swedish Research Council

Department of Perinatal Imaging and Health, King’s College London

National Institute for Health Research

NIHR

Biomedical Research Centre based at Guy's and St Thomas

NHS Foundation Trust and King's College London

Department of Health

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

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