Purinergic Signaling Promotes Proliferation of Adult Mouse Subventricular Zone Cells
Purinergic Signaling Promotes Proliferation of Adult Mouse Subventricular Zone Cells
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DOI：
10.1523/jneurosci.4001-11.2012
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发表时间：
2012-07
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影响因子：
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通讯作者：
S. Suyama;Takehiko Sunabori;H. Kanki;K. Sawamoto;C. Gachet;S. Koizumi;H. Okano
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文献类型：
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作者：
S. Suyama;Takehiko Sunabori;H. Kanki;K. Sawamoto;C. Gachet;S. Koizumi;H. Okano
在成年哺乳动物脑中，神经干细胞（NSCs）存在于脑室下区（SVZ），在那里持续的神经发生持续一生。这些神经干细胞产生神经母细胞，通过形成传递放大细胞迁移到嗅球中，传递放大细胞是神经元谱系的定向前体细胞。在这个SVZ生态位中，由扩散因子进行的细胞间通信以及物理细胞间接触对于调节NSC的增殖和命运决定是重要的。以往的研究表明，细胞外嘌呤能信号，这是由嘌呤化合物，如ATP介导的，在中枢神经系统的细胞间通讯中起着重要的作用。嘌呤能信号也促进成体神经干细胞在体外的增殖。然而，嘌呤能信号在神经原性生态位中的体内作用仍然未知。在这项研究中，ATP输注到小鼠大脑的侧脑室导致SVZ中快速分裂细胞和Mash1阳性传递放大细胞（C型细胞）数量增加。Mash1阳性细胞表达P2Y1嘌呤能信号受体，P2Y1受体特异性拮抗剂MRS 2179的输注减少了快速分裂的溴脱氧尿苷（BrdU）阳性细胞和C型细胞的数量。此外，在P2Y1基因敲除小鼠中观察到快速分裂的BrdU阳性细胞减少17%，Mash1阳性细胞减少19%。总之，这些结果表明，嘌呤能信号通过P2Y1受体促进SVZ小生境中快速分裂细胞和过渡扩增细胞的增殖。
In adult mammalian brains, neural stem cells (NSCs) exist in the subventricular zone (SVZ), where persistent neurogenesis continues throughout life. Those NSCs produce neuroblasts that migrate into the olfactory bulb via formation of transit-amplifying cells, which are committed precursor cells of the neuronal lineage. In this SVZ niche, cell–cell communications conducted by diffusible factors as well as physical cell–cell contacts are important for the regulation of the proliferation and fate determination of NSCs. Previous studies have suggested that extracellular purinergic signaling, which is mediated by purine compounds such as ATP, plays important roles in cell–cell communication in the CNS. Purinergic signaling also promotes the proliferation of adult NSCs in vitro. However, the in vivo roles of purinergic signaling in the neurogenic niche still remain unknown. In this study, ATP infusion into the lateral ventricle of the mouse brain resulted in an increase in the numbers of rapidly dividing cells and Mash1-positive transit-amplifying cells (Type C cells) in the SVZ. Mash1-positive cells express the P2Y1 purinergic signaling receptor and infusion of the P2Y1 receptor-specific antagonist MRS2179 decreased the number of rapidly dividing bromodeoxyuridine (BrdU)-positive cells and Type C cells. Moreover, a 17% reduction of rapidly dividing BrdU-positive cells and a 19% reduction of Mash1-positive cells were observed in P2Y1 knock-out mice. Together, these results suggest that purinergic signaling promotes the proliferation of rapidly dividing cells and transit-amplifying cells, in the SVZ niche through the P2Y1 receptor.