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

Sirko, Swetlana; Schichor, Christian; Della Vecchia, Patrizia; Metzger, Fabian; Sonsalla, Giovanna; Simon, Tatiana; Buerkle, Martina; Kalpazidou, Sofia; Ninkovic, Jovica; Masserdotti, Giacomo; Sauniere, Jean-Frederic; Iacobelli, Valentina; Iacobelli, Stefano; Delbridge, Claire; Hauck, Stefanie M.; Tonn, Jorg-Christian und Goetz, Magdalena (2023): Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain. In: Nature Medicine

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. Intracerebral hemorrhage triggers astrocyte proliferation and mediates neural stem cell potential via Galectin3 signaling.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198