PDGF-B Is Required for Development of the Glymphatic System
PDGF-B Is Required for Development of the Glymphatic System
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DOI：
10.1016/j.celrep.2019.02.050
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发表时间：
2019-03-12
期刊：
影响因子：
8.8
通讯作者：
Lundgaard, Iben
中科院分区：
文献类型：
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作者：
Munk, Anne Sofie;Wang, Wei;Lundgaard, Iben
类淋巴系统是一种高度极化的脑脊液 (CSF) 运输系统，有助于通过全脑血管周围通路网络清除神经毒性分子。在这里，我们绘制了小鼠类淋巴系统的发育图。血管周围的脑脊液运输首先出现在新生小鼠的海马体中，并且在两周龄时在皮质中建立了成熟的类淋巴系统。星形细胞终足的形成和水通道蛋白 4 (AQP4) 的极化表达与血管周围脑脊液转运的出现一致。 PDGF保留基序敲除小鼠品系Pdgfb（ret/ret）中血小板源性生长因子B（PDGF-B）功能的缺陷抑制了类淋巴系统的发育，与野生型小鼠相比，其功能在成年后仍然受到抑制。这些实验描绘了小鼠类淋巴系统的自然发育，并确定了 PDGF-B 在血管周围脑脊液运输发育中的关键作用。
The glymphatic system is a highly polarized cerebro-spinal fluid (CSF) transport system that facilitates the clearance of neurotoxic molecules through a brain-wide network of perivascular pathways. Herein we have mapped the development of the glymphatic system in mice. Perivascular CSF transport first emerges in hippocampus in newborn mice, and a mature glymphatic system is established in the cortex at 2 weeks of age. Formation of astrocytic endfeet and polarized expression of aquaporin 4 (AQP4) consistently co-incided with the appearance of perivascular CSF transport. Deficiency of platelet-derived growth factor B (PDGF-B) function in the PDGF retention motif knockout mouse line Pdgfb(ret/ret) suppressed the development of the glymphatic system, whose functions remained suppressed in adulthood compared with wild-type mice. These experiments map the natural development of the glymphatic system in mice and define a critical role of PDGF-B in the development of perivascular CSF transport.