PDGF-B Is Required for Development of the Glymphatic System

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

doi:10.1016/j.celrep.2019.02.050

PDGF-B Is Required for Development of the Glymphatic System

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^*

^*Corresponding author af dette arbejde

Morphogenesis and Differentiation Program

23 Citationer (Scopus)

42 Downloads (Pure)

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.

Originalsprog	Engelsk
Tidsskrift	Cell Reports
Vol/bind	26
Udgave nummer	11
Sider (fra-til)	2955-2969.e3
Antal sider	15
ISSN	2211-1247
DOI	https://doi.org/10.1016/j.celrep.2019.02.050
Status	Udgivet - 2019

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10.1016/j.celrep.2019.02.050Licens: CC BY-NC-ND

PDGF-B Is Required for Development of the Glymphatic SystemForlagets udgivne version, 5,97 MBLicens: CC BY-NC-ND

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title = "PDGF-B Is Required for Development of the Glymphatic System",

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. ",

keywords = "aquaporin 4, astrocytes, cerebrospinal fluid, glymphatic system, platelet-derived growth factor B, postnatal development",

author = "Munk, {Anne Sofie} and Wei Wang and B{\`e}chet, {Nicholas Burdon} and Eltanahy, {Ahmed M.} and Cheng, {Anne Xiaoan} and Bj{\"o}rn Sigurdsson and Abdellatif Benraiss and M{\"a}e, {Maarja A.} and Kress, {Benjamin Travis} and Kelley, {Douglas H.} and Christer Betsholtz and Kjeld M{\o}llg{\aa}rd and Anja Meissner and Maiken Nedergaard and Iben Lundgaard",

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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 - 2639-1856

VL - 26

SP - 2955-2969.e3

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -

PDGF-B Is Required for Development of the Glymphatic System

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