The Endo-Lysosomal System of Brain Endothelial Cells Is Influenced by Astrocytes In Vitro

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Toth , A E , Siupka , P , Augustine , T J P , Veno , S T , Thomsen , L B , Moos , T , Lohi , H T , Madsen , P , Lykke-Hartmann , K & Nielsen , M S 2018 , ' The Endo-Lysosomal System of Brain Endothelial Cells Is Influenced by Astrocytes In Vitro ' , Molecular Neurobiology , vol. 55 , no. 11 , pp. 8522-8537 .

Title: The Endo-Lysosomal System of Brain Endothelial Cells Is Influenced by Astrocytes In Vitro
Author: Toth, Andrea E.; Siupka, Piotr; Augustine, Thomas J. P.; Veno, Susanne T.; Thomsen, Louiza B.; Moos, Torben; Lohi, Hannes T.; Madsen, Peder; Lykke-Hartmann, Karin; Nielsen, Morten S.
Contributor organization: Research Programs Unit
Research Programme for Molecular Neurology
University of Helsinki
Hannes Tapani Lohi / Principal Investigator
Developmental interactions
Date: 2018-11
Language: eng
Number of pages: 16
Belongs to series: Molecular Neurobiology
ISSN: 0893-7648
Abstract: Receptor- and adsorptive-mediated transport through brain endothelial cells (BEC) of the blood-brain barrier (BBB) involves a complex array of subcellular vesicular structures, the endo-lysosomal system. It consists of several types of vesicles, such as early, recycling, and late endosomes, retromer-positive structures, and lysosomes. Since this system is important for receptor-mediated transcytosis of drugs across brain capillaries, our aim was to characterise the endo-lysosomal system in BEC with emphasis on their interactions with astrocytes. We used primary porcine BEC in monoculture and in co-culture with primary rat astrocytes. The presence of astrocytes changed the intraendothelial vesicular network and significantly impacted vesicular number, morphology, and distribution. Additionally, gene set enrichment analysis revealedthat 60 genes associated with vesicular trafficking showed altered expression in co-cultured BEC. Cytosolic proteins involved in subcellular trafficking were investigated to mark transport routes, such as RAB25 for transcytosis. Strikingly, the adaptor protein called AP1-1B, important for basolateral sorting in epithelial cells, was not expressed in BEC. Altogether, our data pin-point unique features of BEC trafficking network, essentially mapping the endo-lysosomal system of in vitro BBB models. Consequently, our findings constitute a valuable basis for planning the optimal route across the BBB when advancing drug delivery to the brain.
Subject: Blood-brain barrier
Endo-lysosomal system
Porcine brain endothelial cells
Receptor-mediated transcytosis
Vesicular transport
3112 Neurosciences
3124 Neurology and psychiatry
3111 Biomedicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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