Human and mouse cortical astrocytes differ in aquaporin‐4 polarization toward microvessels |
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| Authors: | Vigdis Andersen Eidsvaag Rune Enger Hans‐Arne Hansson Per Kristian Eide Erlend A. Nagelhus |
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| Affiliation: | 1. Department of Neurosurgery, Oslo University Hospital, Rikshospitalet, Oslo, 0027, Norway;2. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;3. GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317 Norway;4. Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, 0027, Norway;5. Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, G?teborg, Sweden;6. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayCorrespondence Per Kristian Eide, MD PhD, Department of Neurosurgery, Oslo University Hospital, Rikshospitalet, POB 4950 Nydalen, N‐0424 Oslo, Norway. Email: |
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| Abstract: | Aquaporin‐4 (AQP4), the predominant water channel in the brain, is expressed in astrocytes and ependymal cells. In rodents AQP4 is highly polarized to perivascular astrocytic endfeet and loss of AQP4 polarization is associated with disease. The present study was undertaken to compare the expression pattern of AQP4 in human and mouse cortical astrocytes. Cortical tissue specimens were sampled from 11 individuals undergoing neurosurgery wherein brain tissue was removed as part of the procedure, and compared with cortical tissue from 5 adult wild‐type mice processed similarly. The tissue samples were immersion‐fixed and prepared for AQP4 immunogold electron microscopy, allowing quantitative assessment of AQP4's subcellular distribution. In mouse we found that AQP4 water channels were prominently clustered around vessels, being 5 to 10‐fold more abundant in astrocytic endfoot membranes facing the capillary endothelium than in parenchymal astrocytic membranes. In contrast, AQP4 was markedly less polarized in human astrocytes, being only two to three‐fold enriched in astrocytic endfoot membranes adjacent to capillaries. The lower degree of AQP4 polarization in human subjects (1/3 of that in mice) was mainly due to higher AQP4 expression in parenchymal astrocytic membranes. We conclude that there are hitherto unrecognized species differences in AQP4 polarization toward microvessels in the cerebral cortex. |
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| Keywords: | AQP4 brain electron microscopy endfeet perivascular |
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