Neuroinflammatory reactive astrocyte formation correlates with adverse outcomes in perinatal white matter injury.


Journal

Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785

Informations de publication

Date de publication:
26 Jun 2024
Historique:
revised: 15 05 2024
received: 07 09 2023
accepted: 20 05 2024
medline: 26 6 2024
pubmed: 26 6 2024
entrez: 26 6 2024
Statut: aheadofprint

Résumé

Perinatal white matter injury (WMI) is the leading cause of long-term neurological morbidity in infants born preterm. Neuroinflammation during a critical window of early brain development plays a key role in WMI disease pathogenesis. The mechanisms linking inflammation with the long-term myelination failure that characterizes WMI, however, remain unknown. Here, we investigate the role of astrocyte reactivity in WMI. In an experimental mouse model of WMI, we demonstrate that WMI disease outcomes are improved in mutant mice lacking secretion of inflammatory molecules TNF-α, IL-1α, and C1q known, in addition to other roles, to induce the formation of a neuroinflammatory reactive astrocyte substate. We show that astrocytes express molecular signatures of the neuroinflammatory reactive astrocyte substate in both our WMI mouse model and human tissue affected by WMI, and that this gene expression pattern is dampened in injured mutant mice. Our data provide evidence that a neuroinflammatory reactive astrocyte substate correlates with adverse WMI disease outcomes, thus highlighting the need for further investigation of these cells as potential causal players in WMI pathology.

Identifiants

pubmed: 38924630
doi: 10.1002/glia.24575
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Dr Miriam and Sheldon G Adelson Medical Research Foundation
Organisme : European Research Council Advanced Grant
ID : 789054
Organisme : NIH HHS
ID : P01NS08351
Pays : United States
Organisme : NIH HHS
ID : R00NS117804
Pays : United States
Organisme : SGGG/Bayer Research Grant 2019
Organisme : UniBE Initiator Award 2020
Organisme : Departmental Research Fund, Department of Obstetrics and Gynecology, Inselspital, Bern
Organisme : NINDS NIH HHS
ID : P01 NS083513
Pays : United States

Informations de copyright

© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.

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Auteurs

Patricia Renz (P)

Department of Obstetrics and Gynecology, Division of Feto-Maternal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.

Marel Steinfort (M)

Department of Obstetrics and Gynecology, Division of Feto-Maternal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.

Valérie Haesler (V)

Department of Obstetrics and Gynecology, Division of Feto-Maternal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.

Vera Tscherrig (V)

Department of Obstetrics and Gynecology, Division of Feto-Maternal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.

Eric J Huang (EJ)

Department of Pathology, UCSF, San Francisco, California, USA.

Manideep Chavali (M)

Department of Pediatrics and Papé Family Pediatric Research Institute, Oregon Health and Science University, Oregon, USA.

Shane Liddelow (S)

Neuroscience Institute, NYU Grossman School of Medicine, New York, New York, USA.
Department of Neuroscience and Physiology, NYU Grossman School of Medicine, New York, New York, USA.
Department of Ophthalmology, NYU Grossman School of Medicine, New York, New York, USA.

David H Rowitch (DH)

Department of Pediatrics, UCSF, San Francisco, California, USA.
Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, UCSF, San Francisco, California, USA.
Newborn Brain Research Institute, UCSF, San Francisco, California, USA.
Department of Paediatrics and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.

Daniel Surbek (D)

Department of Obstetrics and Gynecology, Division of Feto-Maternal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.

Andreina Schoeberlein (A)

Department of Obstetrics and Gynecology, Division of Feto-Maternal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.

Amanda Brosius Lutz (A)

Department of Obstetrics and Gynecology, Division of Feto-Maternal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.

Classifications MeSH