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Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis
- Source :
- Brain-A Journal of Neurology, Brain-A Journal of Neurology, Oxford University Press (OUP), 2021, ⟨10.1093/brain/awab311/6367770⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- Aquaporin 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.
- Subjects :
- Water flow
[SDV]Life Sciences [q-bio]
Aquaporin
Biology
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Homeostasis
Humans
030304 developmental biology
Glia limitans
Aquaporin 4
0303 health sciences
Neurodegeneration
Water
Subcellular localization
medicine.disease
medicine.anatomical_structure
Blood-Brain Barrier
Astrocytes
Glymphatic system
Neurology (clinical)
sense organs
Neuroscience
030217 neurology & neurosurgery
Astrocyte
Subjects
Details
- Language :
- English
- ISSN :
- 00068950 and 14602156
- Database :
- OpenAIRE
- Journal :
- Brain-A Journal of Neurology, Brain-A Journal of Neurology, Oxford University Press (OUP), 2021, ⟨10.1093/brain/awab311/6367770⟩
- Accession number :
- edsair.doi.dedup.....d68443c052ca0c071a44d1007959b02d
- Full Text :
- https://doi.org/10.1093/brain/awab311/6367770⟩