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BACKGROUND: Calcineurin (CaN) is a phosphatase involved in synaptic plasticity. A haplotype of the PPP3CC gene, which encodes the gamma isoform of the catalytic subunit (CaN A), has been associated with schizophrenia. However, the distribution of CaN A gamma is not established, nor whether its expression changes in schizophrenia. METHODS: CaN A expression was analyzed in the hippocampal formation of 13 patients with schizophrenia and 12 controls. All three isoforms were examined, using in situ hybridization histochemistry, RT-PCR, and laser-assisted microdissection. CaN A protein was assessed using ELISA and immunohistochemistry. CaN A mRNAs were also measured in rats treated with haloperidol or chlorpromazine. RESULTS: CaN was prominent in excitatory neurons. CaN A alpha and A beta isoforms were abundant in all subfields, but CaN A gamma was not reliably detected in CA1. CaN A protein, and all three mRNAs, were decreased in schizophrenia. The mRNA reductions were present in all subfields measured, except CA1. CaN A mRNAs were unaltered in the antipsychotic-treated rats. CONCLUSIONS: Decreased CaN expression extends the evidence for aberrant hippocampal synaptic plasticity in schizophrenia, which particularly affects glutamatergic transmission, and which leaves CA1 relatively unaffected. Reduced expression of PPP3CC may underlie its genetic involvement in the disorder.

Original publication

DOI

10.1016/j.biopsych.2004.12.029

Type

Journal article

Journal

Biol Psychiatry

Publication Date

01/04/2005

Volume

57

Pages

702 - 710

Keywords

Aged, Analysis of Variance, Animals, Antipsychotic Agents, Blotting, Northern, Calcineurin, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Hippocampus, Humans, Immunohistochemistry, In Situ Hybridization, Male, Middle Aged, Protein Subunits, RNA, Messenger, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Schizophrenia