Human and mouse cortical astrocytes differ in aquaporin‐4 polarization toward microvessels

• Published in: Glia Vol. 65; no. 6; pp. 964 - 973
• Main Authors: Eidsvaag, Vigdis Andersen, Enger, Rune, Hansson, Hans‐Arne, Eide, Per Kristian, Nagelhus, Erlend A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2017; Wiley-Interscience Publishers; John Wiley and Sons Inc
• Subjects: Adult; Aged; Animals; AQP4; Aquaporin 4 - metabolism; Aquaporins; Astrocytes - metabolism; Astrocytes - ultrastructure; blood-brain-barrier; brain; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - surgery; Cell Membrane - metabolism; Cell Membrane - ultrastructure; cells; Cerebral Cortex - blood supply; Cerebral Cortex - metabolism; Cerebral Cortex - surgery; Cerebral Cortex - ultrastructure; Cohort Studies; electron microscopy; endfeet; Epilepsy - metabolism; Epilepsy - pathology; Epilepsy - surgery; extracellular-space; Female; glial-cells; Humans; immunogold cytochemistry; Immunohistochemistry; Intracranial Aneurysm - metabolism; Intracranial Aneurysm - pathology; Intracranial Aneurysm - surgery; Male; Mice, Inbred C57BL; Microscopy, Electron; Microvessels - metabolism; Microvessels - ultrastructure; Middle Aged; muller; nervous-system; Neurologi; Neurology; perivascular; rat-brain; Rodents; solute transport; water channel protein; Young Adult; perivascular; electron microscopy; endfeet; AQP4; brain
• ISSN: 0894-1491; 1098-1136; 1098-1136
• DOI: 10.1002/glia.23138

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. Main Points Human astrocytes have higher expression of AQP4 water channels in parenchymal membranes than mice The two species have similar AQP4 levels in pericapillary endfeet. Thus, AQP4 polarization towards microvessels is less in humans than in mice.