ISOFORM-SPECIFIC REDISTRIBUTION OF CALCINEURIN A-ALPHA AND A-BETA IN THE HIPPOCAMPAL CA1 REGION OF GERBILS AFTER TRANSIENT ISCHEMIA

To investigate isoform-specific roles of Ca2+/calmodulin-dependent pho sphatase [calcineurin (CaN)] in ischemia-induced cell death, we raised antibodies specific to CaN A alpha and CaN A beta and localized the C aN isoforms in the hippocampal CA1 region of Mongolian gerbils subject ed to a 5-min occlusion of carotid arteries. In the nonischemic gerbil , immunoreactions of both isoforms were highly enriched in CA1 regions , especially in the cytoplasm and apical dendrites of CA1 pyramidal ne urons. At 4-7 days after the induced ischemia, immunoreactivities of t he CaN A alpha isoform in CA1 pyramidal cells were markedly reduced, w hereas they were enhanced in the CA1 radiatum and oriens layers. In co ntrast, CaN A beta immunoreactivities were reduced in all layers of th e ischemic CA1 region, whereas they were enhanced in activated astrocy tes, colocalizing with glial fibrillary acidic protein. These findings suggest that up-regulation of CaN A alpha in afferent fibers in CA1 a nd up-regulation of CaN A beta in reactive astrocytes may be involved in neuronal reorganization after ischemic injury.