title: Molecular evidence of synaptic pathology in the CA1 region in schizophrenia.
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.
authors.affiliation: 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.
authors.forename: Natalie
authors.initials: N
authors.lastname: Matosin
authors.affiliation: 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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fernandez-Enright
authors.affiliation: Departments of Science, Medicine and Health, and Social Sciences, Illawarra Health and Medical Research Institute, University of Wollongong , Wollongong, NSW, Australia.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Lum
authors.affiliation: Departments of Science, Medicine and Health, and Social Sciences, Illawarra Health and Medical Research Institute, University of Wollongong , Wollongong, NSW, Australia.
authors.forename: Martin
authors.identifier: 0000-0001-7602-1340
authors.initials: M
authors.lastname: Engel
authors.affiliation: Departments of Science, Medicine and Health, and Social Sciences, Illawarra Health and Medical Research Institute, University of Wollongong , Wollongong, NSW, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Andrews
authors.affiliation: Departments of Translational Research in Psychiatry and Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry , Munich, Germany.
authors.forename: Nils C
authors.initials: NC
authors.lastname: Gassen
authors.affiliation: Departments of Translational Research in Psychiatry and Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry , Munich, Germany.
authors.forename: Klaus V
authors.initials: KV
authors.lastname: Wagner
authors.affiliation: Departments of Translational Research in Psychiatry and Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry , Munich, Germany.
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.affiliation: Departments of Science, Medicine and Health, and Social Sciences, Illawarra Health and Medical Research Institute, University of Wollongong , Wollongong, NSW, Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Newell