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Disrupted-in-schizophrenia 1 Protein Misassembly Impairs Cognitive Flexibility and Social Behaviors in a Transgenic Rat Model.
Neuroscience
June 2022
Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. Electronic address:
Alterations in cognitive functions, social behaviors and stress reactions are commonly diagnosed in chronic mental illnesses (CMI). Animal models expressing mutant genes associated to CMI represent either rare mutations or those contributing only minimally to genetic risk. Non-genetic causes of CMI can be modeled by disturbing downstream signaling pathways, for example by inducing protein misassembly or aggregation.
View Article and Find Full Text PDFQuantitative Proteomics of Synaptosomal Fractions in a Rat Overexpressing Human DISC1 Gene Indicates Profound Synaptic Dysregulation in the Dorsal Striatum.
Front Mol Neurosci
February 2018
Department of Neuroproteomics, Paracelsus Private Medical University, Salzburg, Austria.
Disrupted-in-schizophrenia 1 (DISC1) is a key protein involved in behavioral processes and various mental disorders, including schizophrenia and major depression. A transgenic rat overexpressing non-mutant human DISC1, modeling aberrant proteostasis of the DISC1 protein, displays behavioral, biochemical and anatomical deficits consistent with aspects of mental disorders, including changes in the dorsal striatum, an anatomical region critical in the development of behavioral disorders. Herein, dorsal striatum of 10 transgenic DISC1 (tgDISC1) and 10 wild type (WT) littermate control rats was used for synaptosomal preparations and for performing liquid chromatography-tandem mass spectrometry (LC-MS)-based quantitative proteomics, using isobaric labeling (TMT10plex).
View Article and Find Full Text PDFMisassembly of non-mutant full-length Disrupted-in-Schizophrenia 1 protein is induced by dopamine in vitro and in vivo.
Mol Psychiatry
November 2016
Department Neuropathology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia.
Sci Rep
October 2016
Institute of Neuropathology, Heinrich Heine University Düsseldorf, Germany.
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.
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