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JCS ePress online publication date 22 Nov 2005
doi: 10.1242/jcs.02680

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Research Article

Involvement of aquaporin-4 in astroglial cell migration and glial scar formation


Samira Saadoun, Marios C. Papadopoulos, Hiroyuki Watanabe, Donghong Yan, Geoffrey T. Manley, and A. S. Verkman*
* Author for correspondence (e-mail: verkman{at}itsa.ucsf.edu)

Aquaporin-4, the major water-selective channel in astroglia throughout the central nervous system, facilitates water movement into and out of the brain. Here, we identify a novel role for aquaporin-4 in astroglial cell migration, as occurs during glial scar formation. Astroglia cultured from the neocortex of aquaporin-4-null mice had similar morphology, proliferation and adhesion, but markedly impaired migration determined by Transwell migration efficiency (18±2 vs 58±4% of cells migrated towards 10% serum in 8 hours; P<0.001) and wound healing rate (4.6 vs 7.0 µm/hour speed of wound edge; P<0.001) compared with wild-type mice. Transwell migration was similarly impaired (25±4% migrated cells) in wild-type astroglia after ~90% reduction in aquaporin-4 protein expression by RNA inhibition. Aquaporin-4 was polarized to the leading edge of the plasma membrane in migrating wild-type astroglia, where rapid shape changes were seen by video microscopy. Astroglial cell migration was enhanced by a small extracellular osmotic gradient, suggesting that aquaporin-4 facilitates water influx across the leading edge of a migrating cell. In an in vivo model of reactive gliosis and astroglial cell migration produced by cortical stab injury, glial scar formation was remarkably impaired in aquaporin-4-null mice, with reduced migration of reactive astroglia towards the site of injury. Our findings provide evidence for the involvement of aquaporin-4 in astroglial cell migration, which occurs during glial scar formation in brain injury, stroke, tumor and focal abscess.
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