Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia



Hamburg, Hannah, Trossbach, Svenja V, Bader, Verian, Chwiesko, Caroline, Kipar, Anja ORCID: 0000-0001-7289-3459, Sauvage, Magdalena, Crum, William R, Vernon, Anthony C, Bidmon, Hans J and Korth, Carsten
(2016) Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia. SCIENTIFIC REPORTS, 6 (1). 34946-.

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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.

Item Type: Article
Uncontrolled Keywords: Brain, Interneurons, Animals, Humans, Rats, Sprague-Dawley, Disease Models, Animal, Parvalbumins, Nerve Tissue Proteins, Magnetic Resonance Imaging, Histocytochemistry, Schizophrenia, Biometry, Gene Expression, Male, Rats, Transgenic, Dopaminergic Neurons
Depositing User: Symplectic Admin
Date Deposited: 07 Feb 2020 11:41
Last Modified: 19 Jan 2023 00:03
DOI: 10.1038/srep34946
Open Access URL: http://doi.org/10.1038/srep34946
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3073961