Interaction between subventricular zone microglia and neural stem cells impacts the neurogenic response in a mouse model of cortical ischemic stroke
After a stroke, the neurogenic response from the subventricular zone (SVZ) to repair the brain is limited. Microglia, as an integral part of the distinctive SVZ microenvironment, control neural stem / precursor cell (NSPC) behavior. Here, we show that discrete stroke-associated SVZ microglial clusters negatively impact the innate neurogenic response, and we propose a repository of relevant microglia-NSPC ligand-receptor pairs. After photothrombosis, a mouse model of ischemic stroke, the altered SVZ niche environment leads to immediate activation of microglia in the niche and an abnormal neurogenic response, with cell-cycle arrest of neural stem cells and neuroblast cell death. Pharmacological restoration of the niche environment increases the SVZ-derived neurogenic repair and microglial depletion increases the formation and survival of newborn neuroblasts in the SVZ. Therefore, we propose that altered cross-communication between microglial subclusters and NSPCs regulates the extent of the innate neurogenic repair response in the SVZ after stroke.
Authors
- Suvra Nath (ORCID: https://orcid.org/0000-0002-0046-9154)
- Roman Sankowski (ORCID: https://orcid.org/0000-0001-9215-8021)
- Christos Galanis (ORCID: https://orcid.org/0000-0002-6469-7201)
- Marco Prinz (ORCID: https://orcid.org/0000-0002-0349-1955)
- Jia-Di Lin
- Andreas Vlachos (ORCID: https://orcid.org/0000-0002-2646-3770)
- Jae K. Lee (ORCID: https://orcid.org/0000-0001-7413-9783)
- James S. Choi (ORCID: https://orcid.org/0000-0002-6392-5268)
- Pasquale Conforti (ORCID: https://orcid.org/0009-0006-8992-1317)
- Lukas Amann (ORCID: https://orcid.org/0000-0002-8363-373X)
- Jose C. Martínez Santamaría
- Sachin S. Deshpande
- Kexin Wu
- Yu‐Hsuan Chu (ORCID: https://orcid.org/0000-0002-7594-321X)
- Christian Schachtrup (ORCID: https://orcid.org/0000-0001-9851-6299)
Institutions
- University of Miami (US)
- University of Freiburg (DE)
- Bernstein Center for Computational Neuroscience Freiburg (DE)
- Brain (Germany) (DE)
- Neurological Surgery (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1038/s41467-024-53217-1
- Citations
- 25
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 6.19
Funders
- Deutsche Forschungsgemeinschaft
- European Synchrotron Radiation Facility
- Albert-Ludwigs-Universität Freiburg
- Else Kröner-Fresenius-Stiftung