ArticleFrontiers in molecular neuroscience2018
Quantitative Proteomics of Synaptosomal Fractions in a Rat Overexpressing Human DISC1 Gene Indicates Profound Synaptic Dysregulation in the Dorsal Striatum.
Article in Frontiers in molecular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 22 citations in OpenAlex.
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- Genetic Influences on Cognitive Dysfunction in Schizophrenia.Current topics in behavioral neurosciences · 2023Article
- What Can We Learn from Animal Models to Study Schizophrenia?Advances in experimental medicine and biology · 2022Article
- Placental DNA methylation changes and the early prediction of autism in full-term newborns.PloS one · 2021Article
- Metabolic Processes are Potential Biological Processes Distinguishing Nonischemic Dilated Cardiomyopathy from Ischemic Cardiomyopathy: A Clue from Serum Proteomics.Pharmacogenomics and personalized medicine · 2021Article
- Genetic deletion ofJournal of psychopharmacology (Oxford, England) · 2020Article
- ANPELA: analysis and performance assessment of the label-free quantification workflow for metaproteomic studies.Briefings in bioinformatics · 2020Article
- Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia.Frontiers in pharmacology · 2020Review
- Role of RGS12 in the differential regulation of kappa opioid receptor-dependent signaling and behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons.PLoS biology · 2019Article
- Dysregulation of a specific immune-related network of genes biologically defines a subset of schizophrenia.Translational psychiatry · 2019Article
- Proteomic Studies Reveal Disrupted in Schizophrenia 1 as a Player in Both Neurodevelopment and Synaptic Function.International journal of molecular sciences · 2018Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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). Functional enrichment analysis was generated from proteins with level changes. The increase in DISC1 expression leads to changes in proteins and synaptic-associated processes including membrane trafficking, ion transport, synaptic organization and neurodevelopment. Canonical pathway analysis assigned proteins with level changes to actin cytoskeleton, Gαq, Rho family GTPase and Rho GDI, axonal guidance, ephrin receptor and dopamine-DARPP32 feedback in cAMP signaling. DISC1-regulated proteins proposed in the current study are also highly associated with neurodevelopmental and mental disorders. Bioinformatics analyses from the current study predicted that the following biological processes may be activated by overexpression of DISC1, i.e., regulation of cell quantities, neuronal and axonal extension and long term potentiation. Our findings demonstrate that the effects of overexpression of non-mutant DISC1 or its misassembly has profound consequences on protein networks essential for behavioral control. These results are also relevant for the interpretation of previous as well as for the design of future studies on DISC1.
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