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

被引:168
作者
Pennington, K. [1 ,2 ]
Beasley, C. L. [3 ]
Dicker, P. [4 ]
Fagan, A. [5 ]
English, J. [1 ]
Pariante, C. M. [6 ]
Wait, R. [7 ]
Dunn, M. J. [2 ]
Cotter, D. R. [1 ]
机构
[1] Royal Coll Surgeons Ireland, Dept Psychiat, Dublin 2, Ireland
[2] Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, Proteome Res Ctr, Dublin 2, Ireland
[3] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada
[4] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin 2, Ireland
[5] Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, Sch Med & Med Sci, Dublin 2, Ireland
[6] Kings Coll London, Sect Stress Psychiat & Immunol, Div Psychol Med, Inst Psychiat, London WC2R 2LS, England
[7] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst, Div Rheumatol, London, England
基金
爱尔兰科学基金会; 英国医学研究理事会; 英国惠康基金;
关键词
two-dimensional gel electrophoresis; schizophrenia; bipolar disorder; septin; synaptic; metabolic;
D O I
10.1038/sj.mp.4002098
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1102 / 1117
页数:16
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