Drebrin Upregulation Regulates Astrocyte Polarization and Supports Tissue Recovery After Spinal Cord Injury in Mice
Spinal cord injury (SCI) results in significant disruption of nerve fibers responsible for transmitting signals between the brain and body, often leading to partial or complete motor, sensory, and autonomic dysfunction below the injury site. Astrocytes are an important component in scar formation, crucial for suppression of injury propagation, effective wound healing, and the regulation of neuronal plasticity. Here, we identify the role of the actin-binding protein Drebrin (DBN) in reactive astrogliosis following SCI. SCI induces the upregulation of DBN in astrocytes, which controls immediate injury containment but also the long-term preservation of tissue integrity and healing in the spinal cord. DBN knockout results in enlarged spinal cord lesions, increased immune cell infiltration, and neurodegeneration. Mechanistically, DBN loss disrupts the polarization of scar border-forming astrocytes, leading to impaired encapsulation of the injury. In summary, DBN serves as a pivotal regulator of SCI outcome by modulating astrocytic polarity, which is essential for establishing a protective barrier confining the lesion site.
Authors
- Barbora Šmejkalová (ORCID: https://orcid.org/0000-0002-4812-9458)
- Jessica C. F. Kwok (ORCID: https://orcid.org/0000-0002-9798-9083)
- James W. Fawcett (ORCID: https://orcid.org/0000-0002-7990-4568)
- Robert Huelse
- Susanne G. Mueller (ORCID: https://orcid.org/0000-0002-5053-2211)
- Marta Ornaghi (ORCID: https://orcid.org/0009-0003-4376-4369)
- Juliane Schiweck (ORCID: https://orcid.org/0000-0001-9319-899X)
- Britta J. Eickholt (ORCID: https://orcid.org/0000-0001-7873-8687)
- Kateřina Štěpánková (ORCID: https://orcid.org/0000-0003-2784-8434)
- Pavla Jendelová (ORCID: https://orcid.org/0000-0002-4644-9212)
- Lucia Machová Urdzíková (ORCID: https://orcid.org/0000-0001-7622-5837)
- Philipp Boehm‐Sturm (ORCID: https://orcid.org/0000-0001-8777-4823)
- Kai Murk (ORCID: https://orcid.org/0000-0002-6573-4529)
Institutions
- University of Leeds (GB)
- Charles University (CZ)
- University of Cambridge (GB)
- German Center for Neurodegenerative Diseases (DE)
- Czech Academy of Sciences, Institute of Experimental Medicine (CZ)
- Institute of Molecular Biology (DE)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Glia
- Published
- 2025-06-11
- DOI
- https://doi.org/10.1002/glia.70048
- Citations
- 4
- Primary Topic
- Spinal Cord Injury Research
- Type
- article
- Field-Weighted Citation Impact
- 5.89
Funders
- Univerzita Karlova v Praze
- European Commission
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Bundesministerium für Bildung und Forschung
- Akademie Věd České Republiky