Decreased hippocampal expression of the susceptibility gene PPP3CC and other calcineurin subunits in schizophrenia.
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.
Eastwood
Sharon L
SL
Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford, United Kingdom. sharon.eastwood@psych.ox.ac.uk
Burnet
Philip W J
PW
Harrison
Paul J
PJ
D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D015152:Blotting, Northern / Q000379:methods; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D014150:Antipsychotic Agents; D021122:Protein Subunits; D012333:RNA, Messenger; D019703:Calcineurin