Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

Pennington, Kyla and Beasley, C. L. and Dicker, P. and Fagin, A. and English , J. and Pariante, C. M. and Wait, R. and Dunn, M. J. and Cotter , D. R. (2008) Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder. Molecular Psychiatry, 13 (12). pp. 1102-1117. ISSN 1359-4184

Full content URL: http://www.nature.com/mp/journal/v13/n12/full/4002...

Documents
Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

Request a copy
[img] PDF
dlPFC_2008_Pennington.pdf - Whole Document
Restricted to Repository staff only

383kB
Item Type:Article
Item Status:Live Archive

Abstract

There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia
and 48 in bipolar disorder were found to be differentially expressed (P < 0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7
of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest
number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.

Additional Information:First published online 16 October 2007
Keywords:two-dimensional gel electrophoresis, schizophrenia, bipolar disorder, septin, synaptic, metabolic
Subjects:C Biological Sciences > C800 Psychology
C Biological Sciences > C860 Neuropsychology
Divisions:College of Social Science > School of Psychology
ID Code:9293
Deposited On:02 May 2013 09:50

Repository Staff Only: item control page