PDGF-B Is Required for Development of the Glymphatic System

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Anne Sofie Munk, Wei Wang, Nicholas Burdon Bèchet, Ahmed M. Eltanahy, Anne Xiaoan Cheng, Björn Sigurdsson, Abdellatif Benraiss, Maarja A. Mäe, Benjamin Travis Kress, Douglas H. Kelley, Christer Betsholtz, Kjeld Møllgård, Anja Meissner, Maiken Nedergaard, Iben Lundgaard

The glymphatic system is a highly polarized cerebrospinal 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 coincided 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.

TidsskriftCell Reports
Udgave nummer11
Sider (fra-til)2955-2969.e3
Antal sider15
StatusUdgivet - 2019

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