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Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder

The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Me...

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Autores principales: Föcking, M, Dicker, P, Lopez, L M, Hryniewiecka, M, Wynne, K, English, J A, Cagney, G, Cotter, D R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290351/
https://www.ncbi.nlm.nih.gov/pubmed/27898073
http://dx.doi.org/10.1038/tp.2016.224
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author Föcking, M
Dicker, P
Lopez, L M
Hryniewiecka, M
Wynne, K
English, J A
Cagney, G
Cotter, D R
author_facet Föcking, M
Dicker, P
Lopez, L M
Hryniewiecka, M
Wynne, K
English, J A
Cagney, G
Cotter, D R
author_sort Föcking, M
collection PubMed
description The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed. Validation of expression changes of DNM1, DTNA, NDUFV2, SEPT11 and SSBP was performed by western blotting. Bioinformatics analysis of the differentially expressed proteins implicated metabolic pathways including mitochondrial function, the tricarboxylic acid cycle, oxidative phosphorylation, protein translation and calcium signaling. The data implicate PSD-associated proteins, and specifically mitochondrial function in bipolar disorder. They relate synaptic function in bipolar disorder and the energy pathways that underpin it. Overall, our findings add to a growing literature linking the PSD and mitochondrial function in psychiatric disorders generally, and suggest that mitochondrial function associated with the PSD is particularly important in bipolar disorder.
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spelling pubmed-52903512017-02-07 Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder Föcking, M Dicker, P Lopez, L M Hryniewiecka, M Wynne, K English, J A Cagney, G Cotter, D R Transl Psychiatry Original Article The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed. Validation of expression changes of DNM1, DTNA, NDUFV2, SEPT11 and SSBP was performed by western blotting. Bioinformatics analysis of the differentially expressed proteins implicated metabolic pathways including mitochondrial function, the tricarboxylic acid cycle, oxidative phosphorylation, protein translation and calcium signaling. The data implicate PSD-associated proteins, and specifically mitochondrial function in bipolar disorder. They relate synaptic function in bipolar disorder and the energy pathways that underpin it. Overall, our findings add to a growing literature linking the PSD and mitochondrial function in psychiatric disorders generally, and suggest that mitochondrial function associated with the PSD is particularly important in bipolar disorder. Nature Publishing Group 2016-11 2016-11-29 /pmc/articles/PMC5290351/ /pubmed/27898073 http://dx.doi.org/10.1038/tp.2016.224 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ 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/
spellingShingle Original Article
Föcking, M
Dicker, P
Lopez, L M
Hryniewiecka, M
Wynne, K
English, J A
Cagney, G
Cotter, D R
Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder
title Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder
title_full Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder
title_fullStr Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder
title_full_unstemmed Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder
title_short Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder
title_sort proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290351/
https://www.ncbi.nlm.nih.gov/pubmed/27898073
http://dx.doi.org/10.1038/tp.2016.224
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