Human and mouse cortical astrocytes differ in aquaporin-4 polarization toward microvessels.
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.
Department of Neurosurgery, Oslo University Hospital, Rikshospitalet, Oslo, 0027, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317, Norway.
Vigdis Andersen
VA
Eidsvaag
GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317, Norway.|Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, 0027, Norway.
Rune
R
Enger
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
Hans-Arne
HA
Hansson
Department of Neurosurgery, Oslo University Hospital, Rikshospitalet, Oslo, 0027, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Per Kristian
PK
Eide
GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317, Norway.|Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, 0027, Norway.
Erlend A
http://orcid.org/0000-0002-8090-4362
EA
Nagelhus
D000328:Adult; D000368:Aged; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism* / Q000601:surgery / Q000648:ultrastructure; D015331:Cohort Studies; D004827:Epilepsy / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D055806:Microvessels / Q000378:metabolism* / Q000648:ultrastructure; D008875:Middle Aged; D055815:Young Adult
C496030:AQP4 protein, human; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4
AQP4; brain; electron microscopy; endfeet; perivascular