Differential expression of calcineurin A subunit mRNA isoforms during rat hippocampal and cerebellar development

Calcineurin (protein phosphatase 2B) is a calcium-dependent serine-threonine phosphatase. It has diverse roles and is centrally involved in synaptic plasticity. The catalytic A subunit of calcineurin has three isoforms, alpha, beta and gamma. Their expression and ontogeny in the brain has not been systematically investigated; such data become important with a report that PPP3CC, the gene encoding calcineurin A gamma, is a susceptibility gene for schizophrenia, and the finding that its expression is decreased in the disorder. We used in situ hybridization histochemistry to measure the relative transcript abundance of calcineurin A gamma and the other catalytic isoforms, A alpha and A beta, during development of the Sprague-Dawley rat hippocampus and cerebellum. All three isoforms are present in both regions at all time points [embryonic day 19 (E19) to postnatal day 42 (P42)] and undergo developmental regulation, but differ in their ontogenic profile. Calcineurin A alpha and A beta mRNAs increased from E19 through to adulthood, whereas A gamma mRNA was most highly expressed during early developmental stages. Calcineurin A alpha and A beta mRNAs positively correlated with synaptophysin mRNA (a synaptic marker), whilst A gamma mRNA was either unrelated to, or negatively correlated, with this transcript. These data confirm that all three calcineurin A subunits are expressed in the rodent brain, and indicate that calcineurin A gamma may have different roles than A alpha and A beta. The data also suggest a potential importance of calcineurin A gamma in neurodevelopment, and in the genetically influenced neurodevelopmental disturbance that is thought to underlie schizophrenia.