Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects with schizophrenia.
BACKGROUND
Deoxyribonucleic acid microarray analyses of dorsolateral prefrontal cortex (DLPFC) area 9 from 10 matched pairs of schizophrenic and control subjects revealed a consistent and significant decrease (p = .001; mean log2 signal difference = -.58) in transcript expression for a gene clone KIAA0417. This database entry has been recently annotated as two highly homologous members of a heat-shock protein family (HSPA12A and HSPA12B).


METHODS
We followed up our initial results by in situ hybridization in subjects with schizophrenia, major depression, and a chronic haloperidol-treated nonhuman primate model. Furthermore, we investigated the distribution of HSPA12A and HSPA12B transcripts across the human and nonhuman primate brain.


RESULTS
We found that HSPA12A (but not HSPA12B) is highly expressed in the human brain and shows a neuron- and region-specific transcript distribution, with strongest expression in the frontal and occipital cortical regions. HSPA12A messenger ribonucleic acid was significantly reduced (p < .01; mean log2 optical density difference = -.84) across subjects with schizophrenia but not in the DLPFC of subjects with major depression or in monkeys chronically treated with haloperidol.


CONCLUSIONS
The data are consistent with metabolic alterations in schizophrenia, reflected in selective changes in the expression of certain genes encoding proteins involved in cellular metabolism or metabolic responsiveness.
Pongrac
Julie L
JL
Department of Psychiatry, E1655 BST, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. karoly+@pitt.edu
Middleton
Frank A
FA
Peng
Lansha
L
Lewis
David A
DA
Levitt
Pat
P
Mirnics
Károly
K
D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D015152:Blotting, Northern / Q000379:methods; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013194:Staining and Labeling
D014150:Antipsychotic Agents; D018840:HSP70 Heat-Shock Proteins; C472130:HSPA12A protein, human; C472131:HSPA12B protein, human; D012333:RNA, Messenger; D006220:Haloperidol