BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex

Morita, Kazuya; Matsumoto, Naoyuki; Saito, K.; Hamabe‐Horiike, Toshihide; Mizuguchi, Keishi; Shinmyo, Yohei; Kawasaki, Hiroshi

doi:10.1038/s41598-021-89997-5

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…We hypothesized that BMP signaling could be critically involved in the regulation of AQP4. BMPs have long been used to promote differentiation of immature astrocytes ( Cheng et al, 2007 ), and it was recently shown that inhibition of BMP signaling in utero reduces the level of AQP4, while overexpression of BMP7 leads to an increase in AQP4 immunofluorescence in the postnatal brain, ( Morita et al, 2021 ). Here we provide evidence that activation of a BMP signaling pathway upregulates AQP4 in matured primary astrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…BMPs are a highly conserved and diverse family of growth factors mainly studied for their roles in development. A recent study has shown that overexpression of BMP7 during development upregulates the expression of AQP4 in the brain through Smad1 phosphorylation ( Morita et al, 2021 ). Other studies have uncovered novel roles for BMPs in the adult CNS coupled to a number of conditions and processes including aging and repair ( Hart and Karimi-Abdolrezaee, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes

Skauli

Savchenko

Ottersen

et al. 2022

Front. Cell. Neurosci.

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Aquaporin-4 (AQP4) is the predominant water channel in the brain; it is enriched in astrocytic foot processes abutting vessels where it is anchored through an interaction with the dystrophin-associated protein (DAP) complex. Enhanced expression with concomitant mislocalization of AQP4 along astrocyte plasma membranes is a hallmark of several neurological conditions. Thus, there is an urgent need to identify which signaling pathways dictate AQP4 microdistribution. Here we show that canonical bone morphogenetic proteins (BMPs), particularly BMP2 and 4, upregulate AQP4 expression in astrocytes and dysregulate the associated DAP complex by differentially affecting its individual members. We further demonstrate the presence of BMP receptors and Smad1/5/9 pathway activation in BMP treated astrocytes. Our analysis of adult mouse brain reveals BMP2 and 4 in neurons and in a subclass of endothelial cells and activated Smad1/5/9 in astrocytes. We conclude that the canonical BMP-signaling pathway might be responsible for regulating the expression of AQP4 and of DAP complex proteins that govern the subcellular compartmentation of this aquaporin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes

Skauli

Savchenko

Ottersen

et al. 2022

Front. Cell. Neurosci.

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Aquaporins in Cardiovascular System

Fan

et al. 2023

Advances in Experimental Medicine and Biology

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Evolutionary changes leading to efficient glymphatic circulation in the mammalian brain

Kameya,

Sakai,

Saito

et al. 2024

Nat Commun

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The functional significance of the morphological and genetic changes that occurred in the brain during evolution is not fully understood. Here we show the relationships between evolutionary changes of the brain and glymphatic circulation. We establish a mathematical model to simulate glymphatic circulation in the cerebral hemispheres, and our results show that cortical neurons accumulate in areas of the cerebral hemispheres where glymphatic circulation is highly efficient. We also find that cortical folds markedly enhance the efficiency of glymphatic circulation in the cerebral hemispheres. Furthermore, our in vivo study using ferrets reveals sulcus-dominant cerebrospinal fluid (CSF) influx, which enhances the efficiency of glymphatic circulation in the enlarged cerebral hemispheres of gyrencephalic brains. Sulcus-dominant CSF influx is mediated by preferential expression of aquaporin-4 in sulcal regions, and similar expression patterns of aquaporin-4 are also found in human cerebral hemispheres. These results indicate that evolutionary changes in the cerebral hemispheres are related to improved efficiency of glymphatic circulation. It seems plausible that the efficiency of glymphatic circulation is an important factor determining the evolutionary trajectory of the cerebral hemispheres.

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BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex

Cited by 3 publications

References 41 publications

Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes

Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes

Aquaporins in Cardiovascular System

Evolutionary changes leading to efficient glymphatic circulation in the mammalian brain

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