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

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
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.

Download full-text


Available from: Karoly Mirnics
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In an effort to find possible new gene candidates involved in the causation of amyotrophic lateral sclerosis (ALS), a prior version of the on-line brain gene expression atlas GENSAT was extensively searched for selectively intense expression within spinal motor neurons. Using autoradiographic data of in-situ hybridization from 3430 genes, a search for selectively intense activity was made for the anterior horn region of murine lumbar spinal cord sectioned in the axial plane. Of 3430 genes, a group of 17 genes was found to be highly expressed within the anterior horn suggesting localization to its primary cellular constituent, the alpha spinal motor neuron. For some genes, an inter-relationship to ALS was already known, such as for heavy, medium, and light neurofilaments, and peripherin. Other genes identified include: Gamma Synuclein, GDNF, SEMA3A, Extended Synaptotagmin-like protein 1, LYNX1, HSPA12a, Cadherin 22, PRKACA, TPPP3 as well as Choline Acetyltransferase, Janus Kinase 1, and the Motor Neuron and Pancreas Homeobox 1. Based on this study, Fibroblast Growth Factor 1 was found to have a particularly selective and intense localization pattern to the ventral horn and may be a good target for development of motor neuron disease therapies; further research is needed.
    Full-text · Article · Apr 2014 · Neurology International
  • Source
    • "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]. "
    [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.
    Full-text · Article · Apr 2013 · Fish & Shellfish Immunology
  • Source
    • "It is unclear why Hspa12a and Hyou1 expression is down-regulated in the cerebrum at both ages in the mutant compared to wild-type mice (Figure 5), but this may be of clinical significance as CACH/VWM symptoms are localized to the cerebrum, while the brainstem is preserved. Interestingly, Hspa12a also shows reduced expression in the prefrontal cortex of subjects with schizophrenia [44]. An additional notable differential expression in the mutant brain is that of Dusp1/Mkp1, which dephosphorylates threonine and tyrosine residues of MAP kinases and inhibits MAPK signaling [45]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in eukaryotic translation initiation factor 2B (eIF2B) cause Childhood Ataxia with CNS Hypomyelination (CACH), also known as Vanishing White Matter disease (VWM), which is associated with a clinical pathology of brain myelin loss upon physiological stress. eIF2B is the guanine nucleotide exchange factor (GEF) of eIF2, which delivers the initiator tRNA(Met) to the ribosome. We recently reported that a R132H mutation in the catalytic subunit of this GEF, causing a 20% reduction in its activity, leads under normal conditions to delayed brain development in a mouse model for CACH/VWM. To further explore the effect of the mutation on global gene expression in the brain, we conducted a wide-scale transcriptome analysis of the first three critical postnatal weeks. Genome-wide mRNA expression of wild-type and mutant mice was profiled at postnatal (P) days 1, 18 and 21 to reflect the early proliferative stage prior to white matter establishment (P1) and the peak of oligodendrocye differentiation and myelin synthesis (P18 and P21). At each developmental stage, between 441 and 818 genes were differentially expressed in the mutant brain with minimal overlap, generating unique time point-specific gene expression signatures. The current study demonstrates that a point mutation in eIF2B, a key translation initiation factor, has a massive effect on global gene expression in the brain. The overall changes in expression patterns reflect multiple layers of indirect effects that accumulate as the brain develops and matures. The differentially expressed genes seem to reflect delayed waves of gene expression as well as an adaptation process to cope with hypersensitivity to cellular stress.
    Full-text · Article · Oct 2011 · PLoS ONE
Show more