DIFFERENTIAL DISTRIBUTION OF CALCINEURIN A-ALPHA ISOENZYME MESSENGER-RNAS IN RAT-BRAIN

Specific antisense oligonucleotide probes for the alpha isoforms of th e catalytic subunit (A-subunit) of calcineurin were prepared and the d istribution of Aalpha1 and Aalpha2 mRNA's has been studied in rat brai n using in situ hybridization histochemistry. Clear regional differenc es have been observed for the Aalpha1 and Aalpha2 isoforms. The predom inant form, Aalpha1, was found to be preferentially expressed in the c audate putamen, the pyramidal cell layer of the hippocampus, specific cortical cell layers, the cerebellar granular cell layer and some othe r brain areas. On the other hand, the Aalpha2 isoform, although being generally less abundant than Aalpha1, gave an intense autoradiography signal in the dentate gyrus of the hippocampus and was the major trans cript in the amygdala, the superior and the inferior colliculus, the c entral gray matter and the reticular formation. These regional differe nces might reflect specific functions exerted by the two alternatively spliced isoenzymes in the CNS and opens the perspective of interferin g with defined calcineurin-dependent signal transduction pathways usin g isoform-specific compounds.