PDGF-B Is Required for Development of the Glymphatic System

TY - JOUR

T1 - PDGF-B Is Required for Development of the Glymphatic System

AU - Munk, Anne Sofie

AU - Wang, Wei

AU - Bèchet, Nicholas Burdon

AU - Eltanahy, Ahmed M.

AU - Cheng, Anne Xiaoan

AU - Sigurdsson, Björn

AU - Benraiss, Abdellatif

AU - Mäe, Maarja A.

AU - Kress, Benjamin Travis

AU - Kelley, Douglas H.

AU - Betsholtz, Christer

AU - Møllgård, Kjeld

AU - Meissner, Anja

AU - Nedergaard, Maiken

AU - Lundgaard, Iben

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - aquaporin 4

KW - astrocytes

KW - cerebrospinal fluid

KW - glymphatic system

KW - platelet-derived growth factor B

KW - postnatal development

U2 - 10.1016/j.celrep.2019.02.050

DO - 10.1016/j.celrep.2019.02.050

M3 - Journal article

C2 - 30865886

AN - SCOPUS:85062401630

SN - 2211-1247

VL - 26

SP - 2955-2969.e3

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -