A functional requirement for astroglia in promoting blood vessel development in the early postnatal brain.
A functional requirement for astroglia in promoting blood vessel development in the early postnatal brain.
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DOI：
10.1371/journal.pone.0048001
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Ma S;Kwon HJ;Huang Z
星形胶质细胞是大脑中的一种主要细胞类型，在大脑发育和功能的许多方面发挥着关键作用。在成人大脑中，星形胶质细胞紧密包裹血管并积极协调局部神经活动和血流。在神经视网膜的发育过程中，血管生长遵循星形胶质细胞过程的网状结构。视网膜星形胶质细胞中还涉及一些基因，用于调节血管发育。这表明星形胶质细胞在促进整个中枢神经系统血管生成中发挥作用。为了确定星形胶质细胞在脑血管生成过程中可能发挥的作用，我们采用遗传方法来抑制围产期皮质生成过程中的星形胶质细胞生成，并检查其对脑血管发育的影响。我们发现，从神经胶质祖细胞中条件性删除orc3（DNA复制所需的基因），可以显着减少脑室下区的神经胶质祖细胞数量和出生后早期大脑皮层中的星形胶质细胞数量。这反过来又导致皮质血管的密度和分支频率严重降低。与血管生长延迟但不退化一致，我们发现在这些突变体中皮质扩张正常化后不同阶段之间血管密度没有显着的净减少，也没有明显的内皮细胞凋亡。此外，伴随着星形胶质细胞相互作用的丧失，我们发现内皮细胞增殖增加，血管腔尺寸扩大以及周细胞中细胞骨架基因表达增强，这表明血管细胞发生了代偿性变化。最后，我们发现突变皮质中的血管形态在星形胶质细胞增生后的后期阶段大幅恢复。因此，这些结果暗示了星形胶质细胞在大脑发育过程中促进血管生长的功能需求。
Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net decreases in vessel density between different stages after normalizing for cortical expansion nor obvious apoptosis of endothelial cells in these mutants. Furthermore, concomitant with loss of astroglial interactions, we find increased endothelial cell proliferation, enlarged vessel luminal size as well as enhanced cytoskeletal gene expression in pericytes, which suggests compensatory changes in vascular cells. Lastly, we find that blood vessel morphology in mutant cortices recovers substantially at later stages, following astrogliosis. These results thus implicate a functional requirement for astroglia in promoting blood vessel growth during brain development.
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影响因子：
8.3
作者：
Ding, Guangliang;Jiang, Quan;Chopp, Michael
通讯作者：
Chopp, Michael
影响因子：
13.9
作者：
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影响因子：
8.3
作者：
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DOI：
10.1523/jneurosci.5648-11.2012
发表时间：
2012-01-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Reichardt LF
影响因子：
16.2
作者：
Malatesta, P;Hack, MA;Götz, M
通讯作者：
Götz, M