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. 2024 May;72(5):938-959.
doi: 10.1002/glia.24512. Epub 2024 Feb 16.

Aquaporin-4 and transient receptor potential vanilloid 4 balance in early postnatal neurodevelopment

Antonio Cibelli  1 , Maria Grazia Mola  1 , Emanuela Saracino  2 , Barbara Barile  1 , Pasqua Abbrescia  3 , Guido Mogni  1 , David C Spray  4 , Eliana Scemes  5 , Andrea Rossi  6 , Diletta Spennato  2 , Maria Svelto  1 , Antonio Frigeri  3   4 , Valentina Benfenati  2 , Grazia Paola Nicchia  1   2   4
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Aquaporin-4 and transient receptor potential vanilloid 4 balance in early postnatal neurodevelopment

Antonio Cibelli et al. Glia. 2024 May.

Abstract

In the adult brain, the water channel aquaporin-4 (AQP4) is expressed in astrocyte endfoot, in supramolecular assemblies, called "Orthogonal Arrays of Particles" (OAPs) together with the transient receptor potential vanilloid 4 (TRPV4), finely regulating the cell volume. The present study aimed at investigating the contribution of AQP4 and TRPV4 to CNS early postnatal development using WT and AQP4 KO brain and retina and neuronal stem cells (NSCs), as an in vitro model of astrocyte differentiation. Western blot analysis showed that, differently from AQP4 and the glial cell markers, TRPV4 was downregulated during CNS development and NSC differentiation. Blue native/SDS-PAGE revealed that AQP4 progressively organized into OAPs throughout the entire differentiation process. Fluorescence quenching assay indicated that the speed of cell volume changes was time-related to NSC differentiation and functional to their migratory ability. Calcium imaging showed that the amplitude of TRPV4 Ca2+ transient is lower, and the dynamics are changed during differentiation and suppressed in AQP4 KO NSCs. Overall, these findings suggest that early postnatal neurodevelopment is subjected to temporally modulated water and Ca2+ dynamics likely to be those sustaining the biochemical and physiological mechanisms responsible for astrocyte differentiation during brain and retinal development.

Keywords: CNS development; aquaporin-4; astrocytes; glia differentiation; neuronal stem cells; orthogonal arrays of particles; transient receptor potential vanilloid 4.

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