Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain.

Abstract:

The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex.

SEEK ID: http://lmmeisd-2.srv.mwn.de/publications/65

PubMed ID: 38066208

DOI: 10.1038/s41591-023-02644-6

Projects: Published Datasets

Publication type: Journal

Journal: Nature medicine

Citation: Nature medicine,29(12):3149-3161

Date Published: 8th Dec 2023

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Registered Mode: manually

Authors: Swetlana Sirko, Christian Schichor, Patrizia Della Vecchia, Fabian Metzger, Giovanna Sonsalla, Tatiana Simon, Martina Bürkle, Sofia Kalpazidou, Jovica Ninkovic, Giacomo Masserdotti, Jean-Frederic Sauniere, Valentina Iacobelli, Stefano Iacobelli, Claire Delbridge, Stefanie M Hauck, Jörg-Christian Tonn, Magdalena Götz

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Citation
Sirko, S., Schichor, C., Della Vecchia, P., Metzger, F., Sonsalla, G., Simon, T., Bürkle, M., Kalpazidou, S., Ninkovic, J., Masserdotti, G., Sauniere, J.-F., Iacobelli, V., Iacobelli, S., Delbridge, C., Hauck, S. M., Tonn, J.-C., & Götz, M. (2023). Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain. In Nature Medicine (Vol. 29, Issue 12, pp. 3149–3161). Springer Science and Business Media LLC. https://doi.org/10.1038/s41591-023-02644-6
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Created: 15th Oct 2024 at 13:00

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