Focal ischemia induces local neurogenesis from astrocytes in adult cortex
Jialei Yang1,2Hong Fan1Junling Xing1Xunyuan Liu1Bo Zhao3Yuanhang Pan1Wenting Wang1Xiufen Zhang1Gang Zhao4Yu-Qiang Ding2Ya-Zhou Wang1
1. Institute of Neurosciences,Fourth Military Medical University2. Key Laboratory of Arrhythmias,Ministry of Education of China,East Hospital,and Department of Anatomy and Neurobiology,Tongji University School of Medicine3. Department of Neurology,Anning Branch of Lanzhou General Hospital of Lanzhou Military Region4. Department of Neurology,Xijing Hospital,Fourth Military Medical University
摘要：Background Adult cortex has long been regarded as "non-neurogenic". Recent studies have indicated the occurrence of neurogenesis in cortex after ischemic stroke. Migrating new-born neurons from the subventricular zone（SVZ） have been demonstrated to contribute to the ischemia-induced neurogenesis in cortex. However, it is still controversial whether local neurogenesis could occur. Here, we investigated this issue by genetic fate mapping, progenitor depletion, and retrovirus labeled patch clamping. Methods and Results Focal ischemia was made by photothrombosis. Co-expression of neural stem cell markers Sox2 and Pax6 with GFAP at the lesion site was found from 3 dpi. Double-staining of BrdU and DCX were observed at 7dpi. Nestin-cre ER:Rosa- DTA mice were used to explore the origin of new-born neurons. Tomoxifen（TAM） was administered either before ischemia to deplete SVZ neural stem cells or post ischemia to deplete cortical Nestin-expressing cells. No significant decrease of cortical Brd U/DCX cells were observed in mice treated with TAM before injury, while significant decrease of Brd U/DCX cells was found in mice treated with TAM after ischemia. To confirm the ischemia-induced local neurogenesis, we injected retrovirus-GFP into the injured cortex of DCX-ds Red mice, and performed whole-cell patch-clamping on dsR ed/GFP double positive cells after ischemia. Action potentials were recorded from about 90% of ds Red/GFP double-positive cells. Further, GFAP-Cre-AAV was injected into the ischemic cortex of Rosa-YFP mice to trace the contribution of astrocytes to the ischemia-induced neurogenesis. Both YFP labeled DCX-positive and Cux1-positive cells were found in the ischemic cortex. Conclusions: These results indicated that focal ischemia can induce a rapid local neurogenesis in adult mice cortex, possibly from resident nestin-positive reactive astrocytes. Our work suggests that endogenous neurogenesis may be amplified for repair after ischemia in the future.