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Cell Rep. 2019 Mar 12;26(11):2955-2969.e3. doi: 10.1016/j.celrep.2019.02.050.

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

Author information

1
Center for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA; Center for Basic and Translational Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark.
2
Center for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA.
3
Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, 221 84 Lund, Sweden.
4
Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, 221 84 Lund, Sweden; Mansoura University Hospital, Faculty of Medicine, Mansoura University, 35516 Mansoura, Egypt.
5
Center for Basic and Translational Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark.
6
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
7
Department of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA.
8
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden; Integrated Cardio Metabolic Center (ICMC), Karolinska Institutet, Novum, 141 57 Huddinge, Sweden.
9
Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
10
Center for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA; Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, 221 84 Lund, Sweden. Electronic address: iben.lundgaard@med.lu.se.

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 Pdgfbret/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

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