This is a summary of Swetlana Sirko, Christian Schichor, Patrizia Della Vecchia, Fabian Metzger, Giovanna Sonsalla,Tatiana Simon, Martina Bürkle, Sofia Kalpazidou, Jovica Ninkovic, Giacomo Masserdotti, Jean Federic Sauniere, Valentina Iacobelli, Stefano Iacobell, Claire Delbridge, Stefanie M. Hauck, Jörg-Christian Tonn, and Magdalena Götz. Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain (2023) https://doi.org/10.1038/s41591-023-02644-6, which appeared in Nature Medicine.
The challenge
Trauma, stroke, epilepsy, and a variety of neurodegenerative diseases lead to irreversible loss of neurons and, consequently, impaired brain function. Glial cells are important in these processes, influencing brain function and disease progression. However, their reaction is injury-specific and can be both beneficial and adverse for disease progression. Previous preclinical studies show that some astrocytes have a protective function and can acquire neural stem cell properties. We wanted to study and identify these reactive astrocytes in human brain and explore in which brain diseases they may exist.
Our approach
We used immunohistochemistry in sections of human brain pathologies with intracerebral hemorrhage, such as stroke, and without, such as meningioma or COVID-19. We also collected samples from epileptogenic regions in patients with epilepsy – with and without cerebral micro-bleedings. We used cell cultures from samples from brains affected by bleeding and created conditions under which neural stem cells would survive and amplify: neurosphere culture conditions.
Our findings
We found that the reactivity of astrocytes is injury-specific. Our results show that proliferating astrocytes in areas that were affected by bleeding expressed Galectin 3, but astrocytes in areas without bleeding didn’t. Proteome analysis identified the protein LGALS3BP, which binds to Galectin 3, as its regulator. This was confirmed by blocking LGALS3BP with an antibody, this stopped cell proliferation and the generation of cells with stem cell properties.
The implications
Identifying Galectin 3 as a novel biomarker for proliferating astrocytes and the Galectin 3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation lays an important cornerstone for future therapies. More importantly, we demonstrated the presence of neural stem cells in the brains of patients with trauma or stroke. Astrocytes have a greater plasticity than expected. This offers an exciting novel cell source for replacing lost neurons.
Creating SyNergies
This research was led by Magdalena Götz from SyNergy together with Swetlana Sirko from LMU. Within SyNergy we now aim to identify the comprehensive molecular signature of these astrocytes in distinct pathologies as well as tools to target them.
