Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects with schizophrenia

Department of Psychiatry, E1655 BST, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. karoly+@pitt.edu
Biological Psychiatry (Impact Factor: 10.26). 12/2004; 56(12):943-50. DOI: 10.1016/j.biopsych.2004.09.005
Source: PubMed


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).
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.
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.
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.

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    • "With regards to moderately intense and selective ventral horn expression of heat shock protein 12a (HSPA12a) as revealed in Figure 1, there is very little information about this protein in the medical literature to interpret its functional significance with respect for spinal motor neurons. However, one study has shown that HSPA12A (but not HSPA12B) is highly expressed in the human brain and shows strongest expression in the frontal and occipital cortical regions;30 significant reductions in HSPA12A messenger ribonucleic acid was found in the prefrontal cortex of subjects that had been affected with schizophrenia. As there are no reports on HSPA12a with respect to motor neurons in health or disease, basic research in this area is needed. "
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    • "Heat shock protein 70 (HSP70) and the translationally controlled tumor protein (TCTP) are both highly conserved protein widely existed in all eukaryotic organisms [3] [4]. Heat shock 70 kDa protein 12A (HSPA12A) is a novel and atypical member of HSP70 family possibly with highly specialized function that might go beyond the HSP chaperone function [5] [6]. The solution structure of TCTP from fission yeast indicated its similarity to a family of small chaperone proteins [3] [7], and a more recent report confirmed that TCTP is a novel HSP with chaperone-like activity [8]. "
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