Dp71 contribution to the molecular scaffold anchoring aquaporine‐4 channels in brain macroglial cells
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- Mehdi Belmaati Cherkaoui
- Université Paris‐Saclay, CNRS, Institut des Neurosciences Paris Saclay Gif‐sur‐Yvette France
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- Ophélie Vacca
- Université Paris‐Saclay, CNRS, Institut des Neurosciences Paris Saclay Gif‐sur‐Yvette France
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- Charlotte Izabelle
- Université Paris‐Saclay, CNRS, Institut des Neurosciences Paris Saclay Gif‐sur‐Yvette France
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- Anne‐Cécile Boulay
- Physiology and Physiopathology of the Gliovascular Unit Research Group, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Unité Mixte de Recherche 7241CNRS, Unité 1050 INSERM PSL Research University Paris France
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- Claire Boulogne
- Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris‐Sud Université Paris‐Saclay Gif‐sur‐Yvette France
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- Cynthia Gillet
- Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris‐Sud Université Paris‐Saclay Gif‐sur‐Yvette France
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- Jean‐Vianney Barnier
- Université Paris‐Saclay, CNRS, Institut des Neurosciences Paris Saclay Gif‐sur‐Yvette France
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- Alvaro Rendon
- UPMC Université Paris 06, INSERM, CNRS, Institut de la Vision Sorbonne Universités Paris France
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- Martine Cohen‐Salmon
- Physiology and Physiopathology of the Gliovascular Unit Research Group, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Unité Mixte de Recherche 7241CNRS, Unité 1050 INSERM PSL Research University Paris France
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- Cyrille Vaillend
- Université Paris‐Saclay, CNRS, Institut des Neurosciences Paris Saclay Gif‐sur‐Yvette France
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説明
<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Intellectual disability in Duchenne muscular dystrophy has been associated with the loss of dystrophin‐protein 71, Dp71, the main dystrophin‐gene product in the adult brain. Dp71 shows major expression in perivascular macroglial endfeet, suggesting that dysfunctional glial mechanisms contribute to cognitive impairments. In the present study, we investigated the molecular alterations induced by a selective loss of Dp71 in mice, using semi‐quantitative immunogold analyses in electron microscopy and immunofluorescence confocal analyses in brain sections and purified gliovascular units. In macroglial pericapillary endfeet of the cerebellum and hippocampus, we found a drastic reduction (70%) of the polarized distribution of aquaporin‐4 (AQP4) channels, a 50% reduction of β‐dystroglycan, and a complete loss of α1‐syntrophin. Interestingly, in the hippocampus and cortex, these effects were not homogeneous: AQP4 and AQP4ex isoforms were mostly lost around capillaries but preserved in large vessels corresponding to pial arteries, penetrating cortical arterioles, and arterioles of the hippocampal fissure, indicating the presence of Dp71‐independent pools of AQP4 in these vascular structures. In conclusion, the depletion of Dp71 strongly alters the distribution of AQP4 selectively in macroglial perivascular endfeet surrounding capillaries. This effect likely affects water homeostasis and blood–brain barrier functions and may thus contribute to the synaptic and cognitive defects associated with Dp71 deficiency.</jats:p></jats:sec>
収録刊行物
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- Glia
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Glia 69 (4), 954-970, 2020-11-28
Wiley
