Decreased hippocampal expression of the susceptibility gene PPP3CC and other calcineurin subunits in schizophrenia

• Published in: Biological psychiatry (1969) Vol. 57; no. 7; pp. 702 - 710
• Main Authors: Eastwood, Sharon L., Burnet, Philip W.J., Harrison, Paul J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2005; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Aged; Analysis of Variance; Animals; Antipsychotic Agents - pharmacology; Biological and medical sciences; Blotting, Northern - methods; Calcineurin; Calcineurin - genetics; Calcineurin - metabolism; Case-Control Studies; Enzyme-Linked Immunosorbent Assay - methods; Female; gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Genetic Predisposition to Disease; hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Immunohistochemistry - methods; In Situ Hybridization - methods; Male; Medical sciences; Middle Aged; mRNA; PPP3CC; protein phosphatase 2B; Protein Subunits - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; mRNA; PPP3CC; hippocampus; Calcineurin; gene expression; protein phosphatase 2B; Human; Enzyme; Phosphoprotein phosphatase; Phosphoric monoester hydrolases; Schizophrenia; Esterases; Gene expression; Subunit; Psychosis; Sensitivity; Messenger RNA; Hydrolases; Hippocampus
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2004.12.029

Calcineurin (CaN) is a phosphatase involved in synaptic plasticity. A haplotype of the PPP3CC gene, which encodes the γ isoform of the catalytic subunit (CaN A), has been associated with schizophrenia. However, the distribution of CaN Aγ is not established, nor whether its expression changes in schizophrenia. 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. CaN was prominent in excitatory neurons. CaN Aα and Aβ isoforms were abundant in all subfields, but CaN Aγ 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. 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.