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Treatment with FK506, an inhibitor of Ca2+/calmodulin dependent phosphatase (calcineurin, CaN), within 1 hr after transient ischemia afforded protection from apoptotic death in CA1 pyramidal neurons. To investigate isoform-specific roles of CaN in the neuronal cell death, we localized CaN A alpha and CaN A beta in the gerbil hippocampus using isoform-specific antibodies. In control gerbils, immunoreactions of both isoforms were highly enriched in hippocampal CA1 pyramidal neurons. Four to seven days after the induced ischemia, immunoreactivities of both isoforms were markedly reduced in the CA1 pyramidal cell and lacunosum-molecular layers. The CaN A alpha immunoreactivity was increased in the CA1 radiatum and oriens layers, whereas that of CaN A beta was enhanced in reactive astrocytes in the CA1 region. These findings suggest that CaN A alpha is involved in sprouting of afferent fibers in CA1 and that CaN A beta is involved in the reaction of astrocytes such as assembly of glial fibril acidic protein.

nihon yakurigaku zasshi/nihon yakurigaku zasshi

Molecular Pathopharmacology of Cellular Responses to Brain Ischemia. Involvement of calcineurin A.ALPHA. a and A.BETA. in neuronal death in a gerbil model of cerebral ischemia.