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Inhibition of Aquaporin 4 Decreases Amyloid A?40 Drainage Around Cerebral Vessels.

ABSTRACT: Aquaporin-4 (AQP4) is located mainly in the astrocytic end-feet around cerebral blood vessels and regulates ion and water homeostasis in the brain. While deletion of AQP4 is shown to reduce amyloid-? (A?) clearance and exacerbate A? peptide accumulation in plaques and vessels of Alzheimer's disease mouse models, the mechanism and clearing pathways involved are debated. Here, we investigated how inhibiting the function of AQP4 in healthy male C57BL/6 J mice impacts clearance of A?40, the more soluble A? isoform. Using two-photon in vivo imaging and visualizing vessels with Sulfurodamine 101 (SR101), we first showed that A?40 injected as a???0.5-?l volume in the cerebral cortex diffused rapidly in parenchyma and accumulated around blood vessels. In animals treated with the AQP4 inhibitor TGN-020, the perivascular A?40 accumulation was significantly (P?

SUBMITTER: Rosu GC

PROVIDER: S-EPMC7515968 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Inhibition of Aquaporin 4 Decreases Amyloid Aβ40 Drainage Around Cerebral Vessels.

Rosu Gabriela-Camelia GC Catalin Bogdan B Balseanu Tudor Adrian TA Laurentiu Mogoanta M Claudiu Margaritescu M Kumar-Singh Samir S Daniel Pirici P

Molecular neurobiology 20200811 11

Aquaporin-4 (AQP4) is located mainly in the astrocytic end-feet around cerebral blood vessels and regulates ion and water homeostasis in the brain. While deletion of AQP4 is shown to reduce amyloid-β (Aβ) clearance and exacerbate Aβ peptide accumulation in plaques and vessels of Alzheimer's disease mouse models, the mechanism and clearing pathways involved are debated. Here, we investigated how inhibiting the function of AQP4 in healthy male C57BL/6 J mice impacts clearance of Aβ40, the more sol ...[more]

PMID: 32783141

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