PDGF-B Is Required for Development of the Glymphatic System

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Abstract

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.

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Munk, A. S., Wang, W., Bèchet, N. B., Eltanahy, A. M., Cheng, A. X., Sigurdsson, B., … Lundgaard, I. (2019). PDGF-B Is Required for Development of the Glymphatic System. Cell Reports, 26(11), 2955-2969.e3. https://doi.org/10.1016/j.celrep.2019.02.050

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