Interaction between subventricular zone microglia and neural stem cells impacts the neurogenic response in a mouse model of cortical ischemic stroke

Suvra Nath, Jose C. Martínez Santamaría, Yu-Hsuan Chu, James S. Choi, Pasquale Conforti, Jia-Di Lin, Roman Sankowski, Lukas Amann, Christos Galanis, Kexin Wu, Sachin S. Deshpande, Andreas Vlachos, Marco Prinz, Jae K. Lee and Christian Schachtrup ()
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Suvra Nath: University of Freiburg
Jose C. Martínez Santamaría: University of Freiburg
Yu-Hsuan Chu: University of Freiburg
James S. Choi: University of Miami School of Medicine
Pasquale Conforti: University of Freiburg
Jia-Di Lin: University of Freiburg
Roman Sankowski: University of Freiburg
Lukas Amann: University of Freiburg
Christos Galanis: University of Freiburg
Kexin Wu: University of Freiburg
Sachin S. Deshpande: University of Freiburg
Andreas Vlachos: University of Freiburg
Marco Prinz: University of Freiburg
Jae K. Lee: University of Miami School of Medicine
Christian Schachtrup: University of Freiburg

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-53217-1

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