title: Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia.
abstract: To date, unequivocal neuroanatomical features have been demonstrated neither for sporadic nor for familial schizophrenia. Here, we investigated the neuroanatomical changes in a transgenic rat model for a subset of sporadic chronic mental illness (CMI), which modestly overexpresses human full-length, non-mutant Disrupted-in-Schizophrenia 1 (DISC1), and for which aberrant dopamine homeostasis consistent with some schizophrenia phenotypes has previously been reported. Neuroanatomical analysis revealed a reduced density of dopaminergic neurons in the substantia nigra and reduced dopaminergic fibres in the striatum. Parvalbumin-positive interneuron occurrence in the somatosensory cortex was shifted from layers II/III to V/VI, and the number of calbindin-positive interneurons was slightly decreased. Reduced corpus callosum thickness confirmed trend-level observations from in vivo MRI and voxel-wise tensor based morphometry. These neuroanatomical changes help explain functional phenotypes of this animal model, some of which resemble changes observed in human schizophrenia post mortem brain tissues. Our findings also demonstrate how a single molecular factor, DISC1 overexpression or misassembly, can account for a variety of seemingly unrelated morphological phenotypes and thus provides a possible unifying explanation for similar findings observed in sporadic schizophrenia patients. Our anatomical investigation of a defined model for sporadic mental illness enables a clearer definition of neuroanatomical changes associated with subsets of human sporadic schizophrenia.
authors.affiliation: Institute of Neuropathology, Heinrich Heine University Düsseldorf, Germany.|Cécile and Oskar Vogt Institute of Brain Research, Heinrich Heine University Düsseldorf, Germany.|Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Switzerland.
authors.forename: Hannah
authors.initials: H
authors.lastname: Hamburg
authors.affiliation: Institute of Neuropathology, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Svenja V
authors.initials: SV
authors.lastname: Trossbach
authors.affiliation: Institute of Neuropathology, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Verian
authors.initials: V
authors.lastname: Bader
authors.affiliation: Functional Architecture of Memory Unit, Mercator Research Group, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chwiesko
authors.affiliation: Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.affiliation: Functional Architecture of Memory Unit, Mercator Research Group, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sauvage
authors.affiliation: King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Neuroimaging, London, United Kingdom.
authors.forename: William R
authors.initials: WR
authors.lastname: Crum
authors.affiliation: King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, London, United Kingdom.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Vernon
authors.affiliation: Cécile and Oskar Vogt Institute of Brain Research, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Bidmon
authors.affiliation: Institute of Neuropathology, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
mesh_terms: D000818:Animals; D001699:Biometry; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000502:physiology*; D015870:Gene Expression; D006651:Histocytochemistry; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010320:Parvalbumins / Q000032:analysis*; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D010320:Parvalbumins