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

AbstractCalcineurin (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, α, β and γ. 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 Aγ, 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 Aγ and the other catalytic isoforms, Aα and Aβ, 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 Aα and Aβ mRNAs increased from E19 through to adulthood, whereas Aγ mRNA was most highly expressed during early developmental stages. Calcineurin Aα and Aβ mRNAs positively correlated with synaptophysin mRNA (a synaptic marker), whilst Aγ 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 Aγ may have different roles than Aα and Aβ. The data also suggest a potential importance of calcineurin Aγ in neurodevelopment, and in the genetically influenced neurodevelopmental disturbance that is thought to underlie schizophrenia.