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.
Biological Psychiatry (Impact Factor: 9.47). 12/2004; 56(12):943-50. DOI: 10.1016/j.biopsych.2004.09.005
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Karoly Mirnics, Jul 05, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heat shock 70kDa protein 12A (HSPA12A) is an atypical member of HSP70 family, and the translationally controlled tumor protein (TCTP) is a novel HSP with chaperone-like activity. They are both involved in protecting organisms against various stressors. In the present study, the cDNAs of HSPA12A and TCTP (called MgHSPA12A and MgTCTP) were identified from Mytilus galloprovincialis by RACE approaches. The full-length cDNA of MgHSPA12A and MgTCTP encoded a peptide of 491 and 171 amino acids, respectively. Real-time PCR was employed to analyze the tissue distribution and temporal expression of these two genes after bacterial challenge and cadmium (Cd) exposure. It was found that the transcripts of MgHSPA12A and MgTCTP were dominantly expressed in gonad and muscle, respectively. The expression level of MgTCTP at 48 h post Vibrio anguillarum challenge was detected to be significantly up-regulated in hepatopancreas (P < 0.05). As concerned to Cd exposure, 2.0-fold increase of MgHSPA12A expression compared to that of the control was observed at 48 h in 5 μg/L Cd(2+)-treated group, while the expression levels of MgTCTP were significantly decreased after exposed to both 5 and 50 μg/L Cd(2+) for 24 h and 96 h. These results suggested the potential involvement of MgHSPA12A and MgTCTP in the mediation of the immune responses and environmental stress in mussels.
    Fish &amp Shellfish Immunology 04/2013; DOI:10.1016/j.fsi.2013.04.021 · 3.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Plentiful data from both animal and human studies support the importance of genetic influences in substance abuse and dependence (Bierut et al., 1998; Tsuang et al., 1998; Kendler et al., 2003). This review summarizes the evidence supporting such genetic influences, places them into perspective regarding animal and human studies, discusses the importance of both genes and environment, and highlights some specific genes of interest regarding the vulnerabilities for problems associated with alcohol use disorders. A long history of repetitive heavy use of alcohol exists across generations as well as the high prevalence of alcohol-related problems in Western societies. Moreover, the information offered here addresses the importance of more general issues regarding genetics and gene expression related to alcohol abuse and dependence.
    British Journal of Pharmacology 06/2008; 154(2):275-87. DOI:10.1038/bjp.2008.88 · 4.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transcriptome profiling using DNA microarrays are data-driven approaches with the potential to uncover unanticipated relationships between gene expression alterations and psychiatric disorders. Studies to date have yielded both convergent and divergent findings. Differences may be explained, at least in part, by the use of a variety of microarray platforms and analytical approaches. Consistent findings across studies suggest, however, that important relationships may exist between altered gene expression and genetic susceptibility to psychiatric disorders. For example, GAD67, RGS4, DTNBP1, NRG1, and GABRAB2 show expression alterations in the postmortem brain of subjects with schizophrenia, and these genes have been also implicated as putative, heritable schizophrenia susceptibility genes. Thus, we propose that for some genes, altered expression in the postmortem human brain may have a dual origin: polymorphisms in the candidate genes themselves or upstream genetic-environmental factors that converge to alter their expression level. We hypothesize that certain gene products, which function as "molecular hubs," commonly show altered expression in psychiatric disorders and confer genetic susceptibility for one or more diseases. Microarray gene expression studies are ideally suited to reveal these putative disease-associated molecular hubs and to identify promising candidates for genetic association studies.
    Biological Psychiatry 08/2006; 60(2):163-76. DOI:10.1016/j.biopsych.2006.02.003 · 9.47 Impact Factor