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Matosin N, Fernandez-Enright F, Lum JS, et al. Molecular evidence of synaptic pathology in the CA1 region in schizophrenia. NPJ Schizophr. 2016;2:16022doi: 10.1038/npjschz.2016.22.
Matosin, N., Fernandez-Enright, F., Lum, J. S., Engel, M., Andrews, J. L., Gassen, N. C., Wagner, K. V., Schmidt, M. V., & Newell, K. A. (2016). Molecular evidence of synaptic pathology in the CA1 region in schizophrenia. NPJ schizophrenia, 216022. https://doi.org/10.1038/npjschz.2016.22
Matosin, Natalie, et al. "Molecular evidence of synaptic pathology in the CA1 region in schizophrenia." NPJ schizophrenia vol. 2 (2016): 16022. doi: https://doi.org/10.1038/npjschz.2016.22
Matosin N, Fernandez-Enright F, Lum JS, Engel M, Andrews JL, Gassen NC, Wagner KV, Schmidt MV, Newell KA. Molecular evidence of synaptic pathology in the CA1 region in schizophrenia. NPJ Schizophr. 2016 Jun 29;2:16022. doi: 10.1038/npjschz.2016.22. eCollection 2016. PMID: 27430010; PMCID: PMC4944906.
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NPJ Schizophr. 2016 Jun 29;2:16022. doi: 10.1038/npjschz.2016.22. eCollection 2016.

Molecular evidence of synaptic pathology in the CA1 region in schizophrenia.

NPJ schizophrenia

Natalie Matosin, Francesca Fernandez-Enright, Jeremy S Lum, Martin Engel, Jessica L Andrews, Nils C Gassen, Klaus V Wagner, Mathias V Schmidt, Kelly A Newell

Affiliations

  1. Departments of Translational Research in Psychiatry and Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany; Departments of Science, Medicine and Health, and Social Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia; Department of Medicine, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
  2. Departments of Science, Medicine and Health, and Social Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia; Department of Health Science, School of Science, Australian Catholic University, Brisbane, QLD, Australia.
  3. Departments of Science, Medicine and Health, and Social Sciences, Illawarra Health and Medical Research Institute, University of Wollongong , Wollongong, NSW, Australia.
  4. Departments of Translational Research in Psychiatry and Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry , Munich, Germany.

PMID: 27430010 PMCID: PMC4944906 DOI: 10.1038/npjschz.2016.22

Abstract

Alterations of postsynaptic density (PSD)95-complex proteins in schizophrenia ostensibly induce deficits in synaptic plasticity, the molecular process underlying cognitive functions. Although some PSD95-complex proteins have been previously examined in the hippocampus in schizophrenia, the status of other equally important molecules is unclear. This is especially true in the cornu ammonis (CA)1 hippocampal subfield, a region that is critically involved in the pathophysiology of the illness. We thus performed a quantitative immunoblot experiment to examine PSD95 and several of its associated proteins in the CA1 region, using post mortem brain samples derived from schizophrenia subjects with age-, sex-, and post mortem interval-matched controls (n=20/group). Our results indicate a substantial reduction in PSD95 protein expression (-61.8%). Further analysis showed additional alterations to the scaffold protein Homer1 (Homer1a: +42.9%, Homer1b/c: -24.6%), with a twofold reduction in the ratio of Homer1b/c:Homer1a isoforms (P=0.011). Metabotropic glutamate receptor 1 (mGluR1) protein levels were significantly reduced (-32.7%), and Preso, a protein that supports interactions between Homer1 or PSD95 with mGluR1, was elevated (+83.3%). Significant reduction in synaptophysin (-27.8%) was also detected, which is a validated marker of synaptic density. These findings support the presence of extensive molecular abnormalities to PSD95 and several of its associated proteins in the CA1 region in schizophrenia, offering a small but significant step toward understanding how proteins in the PSD are altered in the schizophrenia brain, and their relevance to overall hippocampal and cognitive dysfunction in the illness.

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