Apoptosis-induced Wnt2/β-catenin signaling mediates post-ischemic cortical

• 作 者: JialeiYang[1]HongFan[2]JunlingXing[2]BoZhao[3]XunvuanLiu[2]YuanhangPan[2]XiufenZhang[2]WentingWang[2]GangZhao[4]Yu-QiangDing[5]Ya-ZhouWang[2]
• 机 构: Department of Neurobiology and Collaborative Innovation Center for Brain Science,Institute of Neuros
• 出 处: 2015亚太发育生物学国际研讨会
• 发表日期: 2015年期

　　Adult mammalian cortex has long been regarded as "non-neurogenic".Recent studies have reported cortical neurogenesis after cerebral ischemia.However,whether there exists local neurogenesis is still controversial, largely owing to the elusive cellular origin and underlying mechanisms.Here, we present evidence of an apparent transient wave of local neurogenesis, derived mainly from Nestin-positive reactive astrocytes in the cortex following focal ischemia.Our data showed that dying neurons up-regulate and release Wnt2 which activates Wnt/β-catenin signaling in local Nestin-positive cells.Knockdown of Wnt2 and over-expression of dnTCF4 by lentivirus, or genetically depletion of β-catenin in reactive astrocytes can reduce the ischemia-induced cortical neurogenesis.Interestingly, the increase of Wnt2 expression,Wnt signaling activation and cortical neurogenesis are all compromised in Caspase-3 knockout mice.Over-expression of stabilized β-catenin rescues the local neurogenesis in Caspase-3-deficient mice, and stimulates the proliferation of neural progenitors in wild type ischemic cortex.These results indicate a critical role of Caspase-3-dependent Wnt signaling in the ischemia-induced cortical neurogenesis,suggesting that coordination of apoptosis with local neurogenesis may be crucial for neuronal regeneration.