Neural progenitor cells regulate capillary blood flow in the postnatal subventricular zone.
Neural progenitor cells regulate capillary blood flow in the postnatal subventricular zone.
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DOI：
10.1523/jneurosci.1457-12.2012
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发表时间：
2012-11-14
期刊：
影响因子：
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通讯作者：
Bordey A
中科院分区：
文献类型：
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作者：
Lacar B;Herman P;Platel JC;Kubera C;Hyder F;Bordey A
在出生后室下区 (SVZ)，神经祖细胞 (NPC) 进入 S 期与局部血流量增加相关。然而，控制这种血流动力学反应的细胞机制仍然未知。我们发现，SVZ 细胞的一个亚群，即星形胶质细胞样细胞或 B 细胞，在年轻小鼠的 SVZ 毛细血管上发送包裹周细胞的投射。我们使用 P2Y2/4 受体 (P2Y2/4R) 激动剂 UTP、电刺激或在 B 细胞中表达外源 Gq 偶联受体 (MrgA1) 的转基因小鼠，检查了周细胞或 B 细胞中钙的增加是否会导致急性切片中的血管反应。 UTP 增加周细胞中的钙，导致毛细血管收缩。电刺激诱导 SVZ 细胞中的钙增殖，随后涉及嘌呤能受体的毛细血管收缩。在转基因小鼠中，B 细胞中选择性钙增加诱导 P2Y2/4R 依赖性毛细血管收缩，表明 B 细胞释放 ATP 激活周细胞上的嘌呤能受体。有趣的是，在存在 P2Y2/4R 阻滞剂的情况下，观察到扩张。在体内，心室内注射 UTP 会暂时降低使用激光多普勒血流计监测的血流量。使用新生儿电穿孔，我们在慢循环放射状胶质细胞衍生的 B1 细胞（即 NPC）中表达 MrgA1。脑室内注射 MrgA1 配体可增加 SVZ 的血流量。因此，当细胞内钙增加时，B 细胞/NPC 会释放 ATP 和血管舒张因子，激活周细胞上的嘌呤能受体，从而引发体内血管反应和血流量增加。考虑到 NPC 接收来自其他 SVZ 细胞的信号，这些发现进一步表明 NPC 充当 SVZ 中神经代谢耦合的传感器。
In the postnatal subventricular zone (SVZ), S phase entry of neural progenitor cells (NPCs) correlates with a local increase in blood flow. However, the cellular mechanism controlling this hemodynamic response remains unknown. We show that a subpopulation of SVZ cells, i.e. astrocyte-like cells or B cells, send projections ensheathing pericytes on SVZ capillaries in young mice. We examined whether calcium increases in pericytes or B cells led to a vascular response in acute slices using the P2Y2/4 receptor (P2Y2/4R) agonist UTP, electrical stimulation, or transgenic mice expressing exogenous Gq-coupled receptors (MrgA1) in B cells. UTP increased calcium in pericytes leading to capillary constrictions. Electrical stimulation induced calcium propagation in SVZ cells followed by capillary constrictions involving purinergic receptors. In transgenic mice, selective calcium increases in B cells induced P2Y2/4R-dependent capillary constrictions, suggesting that B cells release ATP activating purinergic receptors on pericytes. Interestingly, in the presence of a P2Y2/4R blocker, a dilation was observed. In vivo, intraventricular UTP injection transiently decreased blood flow monitored using laser Doppler flowmetry. Using neonatal electroporation, we expressed MrgA1 in slow cycling radial glia-derived B1 cells, i.e. NPCs. Intraventricular injection of a MrgA1 ligand increased blood flow in the SVZ. Thus, upon intracellular calcium increases B cells/NPCs release ATP and vasodilating factors that activate purinergic receptors on pericytes triggering a vascular response and blood flow increase in vivo. Considering that NPCs receive signals from other SVZ cells, these findings further suggest that NPCs act as transducers of neurometabolic coupling in the SVZ.