cad a22 4500 467973849 20181103044556.0 cr unu---uuuuu 170328s2016 xx s 000 0 eng 10.5167/uzh-136439 doi 10.1038/srep34946 doi (ZORA)oai:www.zora.uzh.ch:136439 570 ddc 27721451 pmid Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia [Elektronische Daten] [Hannah Hamburg, Svenja V Trossbach, Verian Bader, Caroline Chwiesko, Anja Kipar, Magdalena Sauvage, William R Crum, Anthony C Vernon, Hans J Bidmon, Carsten Korth] openAccess eu-repo 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. Institute of Veterinary Pathology zora Hamburg Hannah joint author Trossbach Svenja V. joint author Bader Verian joint author Chwiesko Caroline joint author Kipar Anja joint author Sauvage Magdalena joint author Crum William R. joint author Vernon Anthony C. joint author Bidmon Hans J. joint author Korth Carsten joint author Scientific Reports 6(1):34946 https://www.zora.uzh.ch/id/eprint/136439/1/Kipar_Simultaneous_effects_on_Journal_Nature.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/136439/1/Kipar_Simultaneous_effects_on_Journal_Nature.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Hamburg Hannah joint author ZORA 700 1- Trossbach Svenja V. joint author ZORA 700 1- Bader Verian joint author ZORA 700 1- Chwiesko Caroline joint author ZORA 700 1- Kipar Anja joint author ZORA 700 1- Sauvage Magdalena joint author ZORA 700 1- Crum William R. joint author ZORA 700 1- Vernon Anthony C. joint author ZORA 700 1- Bidmon Hans J. joint author ZORA 700 1- Korth Carsten joint author ZORA 773 0- Scientific Reports 6(1):34946 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess