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A postmortem analysis of NMDA ionotropic and group 1 metabotropic glutamate receptors in the nucleus accumbens in schizophrenia.

Journal Article


Abstract


  • Background

    The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort.

    Methods

    We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms). In addition, we measured the group 1 mGluR endogenous regulators, neurochondrin and Homer1b/c, which have recently been implicated in the pathophysiology of schizophrenia.

    Results

    Protein levels of glutamatergic receptors and endogenous regulators were not significantly different between the controls and individuals who had schizophrenia. Furthermore, mGluR5, but not mGluR1, showed a positive association with NMDA receptor subunits, suggesting differential interactions between these receptors in this brain region.

    Limitations

    Investigation of these proteins in antipsychotic-naive individuals, in addition to the subregions of the NAcc and subcellular fractions, will strengthen future studies.

    Conclusion

    The present study does not provide evidence for glutamatergic abnormalities within the NAcc of individuals with schizophrenia. Taken together with the results of previous studies, these findings suggest NMDA receptors and group 1 mGluRs are altered in a brain region-dependent manner in individuals with schizophrenia. The differential associations between mGluR1, mGluR5 and NMDA receptors observed in this study warrant further research into the interactions of these proteins and the implications for the therapeutic and adverse effect profile of glutamatergic-based novel therapeutics.

Publication Date


  • 2018

Citation


  • Lum, J. S., Millard, S. J., Huang, X. -F., Ooi, L., & Newell, K. A. (2018). A postmortem analysis of NMDA ionotropic and group 1 metabotropic glutamate receptors in the nucleus accumbens in schizophrenia.. Journal of psychiatry & neuroscience : JPN, 43(2), 102-110. doi:10.1503/jpn.170077

Web Of Science Accession Number


Start Page


  • 102

End Page


  • 110

Volume


  • 43

Issue


  • 2

Abstract


  • Background

    The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort.

    Methods

    We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms). In addition, we measured the group 1 mGluR endogenous regulators, neurochondrin and Homer1b/c, which have recently been implicated in the pathophysiology of schizophrenia.

    Results

    Protein levels of glutamatergic receptors and endogenous regulators were not significantly different between the controls and individuals who had schizophrenia. Furthermore, mGluR5, but not mGluR1, showed a positive association with NMDA receptor subunits, suggesting differential interactions between these receptors in this brain region.

    Limitations

    Investigation of these proteins in antipsychotic-naive individuals, in addition to the subregions of the NAcc and subcellular fractions, will strengthen future studies.

    Conclusion

    The present study does not provide evidence for glutamatergic abnormalities within the NAcc of individuals with schizophrenia. Taken together with the results of previous studies, these findings suggest NMDA receptors and group 1 mGluRs are altered in a brain region-dependent manner in individuals with schizophrenia. The differential associations between mGluR1, mGluR5 and NMDA receptors observed in this study warrant further research into the interactions of these proteins and the implications for the therapeutic and adverse effect profile of glutamatergic-based novel therapeutics.

Publication Date


  • 2018

Citation


  • Lum, J. S., Millard, S. J., Huang, X. -F., Ooi, L., & Newell, K. A. (2018). A postmortem analysis of NMDA ionotropic and group 1 metabotropic glutamate receptors in the nucleus accumbens in schizophrenia.. Journal of psychiatry & neuroscience : JPN, 43(2), 102-110. doi:10.1503/jpn.170077

Web Of Science Accession Number


Start Page


  • 102

End Page


  • 110

Volume


  • 43

Issue


  • 2