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The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review

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Title: The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review
Authors: Dahoun, T
Trossbach, SV
Brandon, NJ
Korth, C
Howes, O
Item Type: Journal Article
Abstract: Although the Disrupted-in-Schizophrenia 1 (DISC1) was found as a risk gene that may account for mental symptoms of a specific pedigree in the past, it is now known as a risk biological factor for mental illnesses possibly associated with dopamine impairments. DISC1 is a scaffold protein interacting with proteins involved in the dopamine system. Here, we summarize the impact of DISC1 disruption on the dopamine system in animal models, considering its effects on presynaptic dopaminergic function (tyrosine hydroxylase levels, dopamine transporter levels, dopamine levels at baseline and after amphetamine administration), and post-synaptic dopaminergic function (dopamine D1 and D2 receptor levels, dopamine receptor binding potential, and locomotor activity after amphetamine administration). Our findings show that many, but not all DISC1 models display 1) increased locomotion after amphetamine administration 2) increased dopamine levels after amphetamine administration in the nucleus accumbens 3) inconsistent basal dopamine levels, dopamine receptor levels and binding potentials. There is also limited evidence for decreased tyrosine hydroxylase levels in the frontal cortex and increased dopamine transporter levels in the striatum but not nucleus accumbens, but these conclusions warrant further replication. The main dopaminergic findings are seen across different DISC1 models, providing convergent evidence that DISC1 has a role in regulating dopaminergic function. These results implicate dopaminergic dysregulation as a mechanism underlying the increased rate of schizophrenia seen in DISC1 variant carriers, and provide insights into how Disc1, and potentially DISC1-interacting proteins such as Akt and GSK-3, could be used as novel therapeutic targets for schizophrenia.
Issue Date: 31-Jan-2017
Date of Acceptance: 27-Nov-2016
URI: http://hdl.handle.net/10044/1/42799
DOI: https://dx.doi.org/10.1038/tp.2016.282
ISSN: 2158-3188
Publisher: Nature Publishing Group
Journal / Book Title: Translational Psychiatry
Volume: 7
Copyright Statement: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 607616
Keywords: Science & Technology
Life Sciences & Biomedicine
Psychiatry
POSITRON-EMISSION-TOMOGRAPHY
MAJOR MENTAL-ILLNESS
INDUCED LOCOMOTOR-ACTIVITY
GENETIC RISK-FACTOR
NUCLEUS-ACCUMBENS
DEPRESSED-PATIENTS
MOUSE MODELS
MUTANT MICE
PROGENITOR PROLIFERATION
BEHAVIORAL DEFICITS
Publication Status: Published
Article Number: e1015
Appears in Collections:Clinical Sciences
Imaging Sciences
Faculty of Medicine



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