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Expression of the Hippocampal NMDA Receptor GluN1 Subunit and Its Splicing Isoforms in Schizophrenia: Postmortem Study

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Abstract

There is accumulating evidence that disturbances in N-methyl-d-aspartate receptor (NMDA-R) functioning are associated with the pathogenesis of schizophrenia. To assess actual changes in the expression of the GluN1 subunit and its isoforms, we measured absolute differences in the levels of mRNA/protein for panGluN1 (eight isoforms altogether) as well as the mRNA individual isoforms in the postmortem left/right hippocampus of patients with schizophrenia in comparison with non-psychiatric subjects. There were no significant differences in the panGluN1 subunit mRNA expression, but the absolute left/right differences were much more pronounced in the patients with schizophrenia. Protein levels of the GluN1 subunit in the left hippocampus in male schizophrenic patients were lower than controls. The expression of the NR1-4b isoform was attenuated in the left, whereas the NR1-2b was reduced in the right hippocampus of schizophrenic patients. Isoforms associated with the efficiency of NMDA-induced gene expression and with phosphorylation occurred more commonly in schizophrenic hippocampi. In summary, our study suggests that NMDA-R hypofunction in schizophrenia might be selectively dependent on the dysregulation of GluN1 subunit expression, which exhibits a somewhat different expression in the left/right hippocampus of psychotic patients.

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Acknowledgments

The research was supported by the Projects MZ00PCP2005 and IGA MZCR NR/9324. The authors thank Dr. Emerich Majer (Department of Pathology, Prague Mental Hospital Bohnice, Czech Rep.) for taking samples and Prof. Martin Alda MD, FRCPC (Dalhousie University, Halifax, Canada) for helpful comments.

Declaration of Interest

The authors have no conflicts of interest or financial disclosures, related directly or indirectly to this study.

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Authors and Affiliations

  1. Prague Psychiatric Center, Ustavni 91, 181 03, Prague 8, Czech Republic

    Monika Vrajová, Jiří Horáček & Cyril Höschl

  2. Institute of Physiology, Academy of Sciences, Prague, Czech Republic

    František Šťastný

  3. Institute of Computer Science, Academy of Sciences, Prague, Czech Republic

    Jan Klaschka

  4. Faculty of Science, Institute of Biochemistry, Brno, Czech Republic

    Jan Lochman & Omar Šerý

  5. Laboratory of DNA Diagnostics, Hospital Na Homolce, Prague, Czech Republic

    Soňa Peková

Authors
  1. Monika Vrajová
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  2. František Šťastný
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  3. Jiří Horáček
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  4. Jan Lochman
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Correspondence to Monika Vrajová.

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Vrajová, M., Šťastný, F., Horáček, J. et al. Expression of the Hippocampal NMDA Receptor GluN1 Subunit and Its Splicing Isoforms in Schizophrenia: Postmortem Study. Neurochem Res 35, 994–1002 (2010). https://doi.org/10.1007/s11064-010-0145-z

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  • DOI: https://doi.org/10.1007/s11064-010-0145-z

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