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Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis

dc.contributor.authorSALMAN, Mootaz
dc.contributor.authorKITCHEN, Philip
dc.contributor.authorHALSEY, Andrea
dc.contributor.authorWANG, Marie Xun
dc.contributor.authorTORNROTH-HORSEFIELD, Susanna
dc.contributor.authorCONNER, Alex
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBADAUT, Jerome
dc.contributor.authorILIFF, Jeffrey
dc.contributor.authorBILL, Roslyn
dc.date.accessioned2021-10-07T16:27:24Z
dc.date.available2021-10-07T16:27:24Z
dc.date.issued2021-09-10
dc.identifier.issn0006-8950
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112559
dc.description.abstractEnAquaporin channels facilitate bidirectional water flow in all cells and tissues. AQP4 is highly expressed in astrocytes. In the CNS, it is enriched in astrocyte endfeet, at synapses, and at the glia limitans, where it mediates water exchange across the blood-spinal cord and blood-brain barriers (BSCB/BBB), and controls cell volume, extracellular space volume, and astrocyte migration. Perivascular enrichment of AQP4 at the BSCB/BBB suggests a role in glymphatic function. Recently, we have demonstrated that AQP4 localization is also dynamically regulated at the subcellular level, affecting membrane water permeability. Ageing, cerebrovascular disease, traumatic CNS injury, and sleep disruption are established and emerging risk factors in developing neurodegeneration, and in animal models of each, impairment of glymphatic function is associated with changes in perivascular AQP4 localization. CNS oedema is caused by passive water influx through AQP4 in response to osmotic imbalances. We have demonstrated that reducing dynamic relocalization of AQP4 to the BSCB/BBB reduces CNS oedema, and accelerates functional recovery in rodent models. Given the difficulties in developing pore-blocking AQP4 inhibitors, targeting AQP4 subcellular localization opens up new treatment avenues for CNS oedema, neurovascular and neurodegenerative diseases, and provides a framework to address fundamental questions about water homeostasis in health and disease.
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.title.enEmerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis
dc.typeArticle de revue
dc.identifier.doi10.1093/brain/awab311/6367770
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalBrain - A Journal of Neurology
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536*
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-03366666
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03366666v1
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