Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury

摘要

We reported previously that astroglia cultured from aquaporin-4-deficient ( AQP4(-/-)) mice migrate more slowly in vitro than those from wild-type ( AQP4(-/-)) mice ( J. Cell Sci. 2005; 118, 5691 - 5698). Here, we investigate the migration of fluorescently labeled AQP4(-/-) and AQP4(-/-) astroglia after implantation into mouse brains in which directional movement was stimulated by a planar stab wound 3 mm away from the axis of the injection needle. Two days after cell injection we determined the location, elongation ratio, and orientation of labeled cells. Migration of AQP4(+/+) but not AQP4(-/-) cells toward the stab was greater than away from the stab. AQP4(-/-) astroglia moved on average 1.5 mm toward the stab compared with 0.6 mm for AQP4(-/-) cells. More than 25 of the migrating AQP4(-/-) cells but 2.5). In transwell assays, AQP4(-/-) astroglia migrated faster than AQP4(-/-) cells in a manner dependent on pore size. At 8 h, similar to 50 of AQP4(-/-) cells migrated through 8-mu m diameter pores, whereas equivalent migration of AQP4(-/-) cells was found for 12-mu m diameter pores. These results provide in vivo evidence for AQP4-dependent astroglial migration and suggest that modulation of AQP4 expression or function might alter glial scarring.