GDF15 promotes simultaneous astrocyte remodeling and tight junction strengthening at the blood-brain barrier.
GDF15
RRID:AB_10753223
RRID:AB_2242334
RRID:AB_2534069
RRID:AB_258785
RRID:AB_297817
RRID:AB_477010
RRID:AB_732535
RRID:RGD_13508588
RRID:SCR_003070
astrocytes
blood-brain barrier
remodeling
tight junctions
Journal
Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
18
09
2019
revised:
24
01
2020
accepted:
24
02
2020
pubmed:
15
3
2020
medline:
27
8
2021
entrez:
15
3
2020
Statut:
ppublish
Résumé
Perivascular astrocyte processes (PAP) surround cerebral endothelial cells (ECs) and modulate the strengthening of tight junctions to influence blood-brain barrier (BBB) permeability. Morphologically altered astrocytes may affect barrier properties and trigger the onset of brain pathologies. However, astrocyte-dependent mediators of these events remain poorly studied. Here, we show a pharmacologically driven elevated expression and release of growth/differentiation factor 15 (GDF15) in rat primary astrocytes and cerebral PAP. GDF15 has been shown to possess trophic properties for motor neurons, prompting us to hypothesize similar effects on astrocytes. Indeed, its increased expression and release occurred simultaneously to morphological changes of astrocytes in vitro and PAP, suggesting modulatory effects of GDF15 on these cells, but also neighboring EC. Administration of recombinant GDF15 was sufficient to promote astrocyte remodeling and enhance barrier properties between ECs in vitro, whereas its pharmacogenetic abrogation prevented these effects. We validated our findings in male high anxiety-related behavior rats, an animal model of depressive-like behavior, with shrunk PAP associated with reduced expression of the junctional protein claudin-5, which were both restored by a pharmacologically induced increase in GDF15 expression. Thus, we identified GDF15 as an astrocyte-derived trigger of astrocyte process remodeling linked to enhanced tight junction strengthening at the BBB.
Substances chimiques
Gdf15 protein, rat
0
Growth Differentiation Factor 15
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1433-1456Informations de copyright
© 2020 Wiley Periodicals, Inc.
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