Wicki-Stordeur Leigh E, Sanchez-Arias Juan C, Dhaliwal Jagroop, Carmona-Wagner Esther O, Shestopalov Valery I, Lagace Diane C, Swayne Leigh Anne
Division of Medical Sciences, University of Victoria, Victoria, British Columbia V8P 5C2, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
J Neurosci. 2016 Jan 27;36(4):1203-10. doi: 10.1523/JNEUROSCI.0436-15.2016.
We demonstrated previously that Pannexin 1 (Panx1), an ion and metabolite channel, promotes the growth and proliferation of ventricular zone (VZ) neural precursor cells (NPCs) in vitro. To investigate its role in vivo, we used floxed Panx1 mice in combination with viruses to delete Panx1 in VZ NPCs and to track numbers of Panx1-null and Panx1-expressing VZ NPCs over time. Two days after virus injection, Panx1-null cells were less abundant than Panx1-expressing cells, suggesting that Panx1 is required for the maintenance of VZ NPCs. We also investigated the effect of Panx1 deletion in VZ NPCs after focal cortical stroke via photothrombosis. Panx1 is essential for maintaining elevated VZ NPC numbers after stroke. In contrast, Panx1-null NPCs were more abundant than Panx1-expressing NPCs in the peri-infarct cortex. Together, these findings suggest that Panx1 plays an important role in NPC maintenance in the VZ niche in the naive and stroke brain and could be a key target for improving NPC survival in the peri-infarct cortex.
Here, we demonstrate that Pannexin 1 (Panx1) maintains a consistent population size of neural precursor cells in the ventricular zone, both in the healthy brain and in the context of stroke. In contrast, Panx1 appears to be detrimental to the survival of neural precursor cells that surround damaged cortical tissue in the stroke brain. This suggests that targeting Panx1 in the peri-infarct cortex, in combination with other therapies, could improve cell survival around the injury site.
我们之前证明，离子和代谢物通道泛连接蛋白1（Panx1）可促进体外脑室区（VZ）神经前体细胞（NPC）的生长和增殖。为了研究其在体内的作用，我们将携带floxed Panx1的小鼠与病毒联合使用，以删除VZ NPC中的Panx1，并追踪随着时间推移Panx1缺失和表达Panx1的VZ NPC的数量。病毒注射两天后，Panx1缺失的细胞比表达Panx1的细胞数量少，这表明Panx1是维持VZ NPC所必需的。我们还通过光血栓形成研究了局灶性皮质中风后VZ NPC中Panx1缺失的影响。Panx1对于中风后维持升高的VZ NPC数量至关重要。相比之下，在梗死周围皮层中，Panx1缺失的NPC比表达Panx1的NPC数量更多。总之，这些发现表明，Panx1在正常和中风脑的VZ生态位中NPC的维持中起重要作用，并且可能是改善梗死周围皮层中NPC存活的关键靶点。
在这里，我们证明泛连接蛋白1（Panx1）在健康脑和中风情况下均维持脑室区神经前体细胞的一致群体大小。相比之下，Panx1似乎对中风脑中受损皮质组织周围的神经前体细胞存活有害。这表明在梗死周围皮层中靶向Panx1并结合其他疗法，可以改善损伤部位周围的细胞存活。
