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                                                          4. Greater plasticity than expected: Astrocytes proliferate and acquire neural stem cell properties after brain injury
                                                          News | 13/12/2023 | Research Spotlight

                                                          Greater plasticity than expected: Astrocytes proliferate and acquire neural stem cell properties after brain injury

                                                          Glial cells play an important role in brain injuries; they can support brain function and react to the injury. Researchers found that astrocytes, a specific type of glial cells, proliferate and acquire neural stem cell properties after brain injury. They identified the Galectin 3 binding protein LGALS3BP as a regulator of these cells. Their discovery shows that astrocytes have a greater plasticity than expected and offers a novel source for replacing lost neurons. 

                                                          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. 

                                                          Participating Universities
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                                                          SyNergy is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the German Excellence Strategy (EXC 2145 SyNergy – ID 390857198). The Excellence Strategy promotes outstanding research at German universities. 

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                                                          Munich Cluster for Systems Neurology (SyNergy)

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