Proteomic analysis reveals protein changes within layer 2 of the insular cortex in schizophrenia

被引:58
作者
Pennington, Kyla [1 ,2 ]
Dicker, Patrick
Dunn, Michael J. [2 ]
Cotter, David 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, Ireland
基金
英国惠康基金; 爱尔兰科学基金会;
关键词
2-DE; Insular cortex; Layer; 2; Neuronal plasticity; Schizophrenia;
D O I
10.1002/pmic.200800415
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Abnormalities in the size and activity of the insular cortex (IC), a brain region involved in auditory hallucinations and language, have been previously found in brain imaging studies in schizophrenia. In addition, cortical layer 2 has been shown to be abnormal in many brain regions in schizophrenia. In this study, 2-D DIGE was used to quantitatively analyse protein expression in schizophrenia and control cases (n = 15/group) in microdissected layer 2 IC tissue. Proteomic analyses revealed 57 significantly differentially expressed (p<0.05) protein spots in schizophrenia. Validation of differential expression of two of the proteins differentially expressed was subsequently confirmed using Western blotting. This work provides evidence of abnormal protein expression in layer 2 of the IC in schizophrenia, supporting previous work of reduced neuronal size in this cortical layer in the IC. Over half of proteins abnormally expressed in this study have not been reported previously in proteomic studies investigating schizophrenia or neurodegenerative disorders. Proteins found to be abnormally expressed appear to collectively impact on neuronal plasticity through roles in neurite outgrowth, cellular morphogenesis and synaptic function.
引用
收藏
页码:5097 / 5107
页数:11
相关论文
共 57 条
[1]   A novel experimental design for comparative two-dimensional gel analysis: Two-dimensional difference gel electrophoresis incorporating a pooled internal standard [J].
Alban, A ;
David, SO ;
Bjorkesten, L ;
Andersson, C ;
Sloge, E ;
Lewis, S ;
Currie, I .
PROTEOMICS, 2003, 3 (01) :36-44
[2]   Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia [J].
Ardekani, BA ;
Bappal, A ;
D'Angelo, D ;
Ashtari, M ;
Lencz, T ;
Szeszko, PR ;
Butler, PD ;
Javitt, DC ;
Lim, KO ;
Hrabe, J ;
Nierenberg, J ;
Branch, CA ;
Hoptman, MJ .
NEUROREPORT, 2005, 16 (13) :1455-1459
[3]   Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging [J].
Bagary, MS ;
Symms, MR ;
Barker, GJ ;
Mutsatsa, SH ;
Joyce, EM ;
Ron, MA .
ARCHIVES OF GENERAL PSYCHIATRY, 2003, 60 (08) :779-788
[4]   Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins [J].
Beasley, CL ;
Zhang, ZJ ;
Patten, I ;
Reynolds, GP .
BIOLOGICAL PSYCHIATRY, 2002, 52 (07) :708-715
[5]   Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: Evidence for disease-associated changes [J].
Beasley, Clare L. ;
Pennington, Kyla ;
Behan, Aine ;
Wait, Robin ;
Dunn, Michael J. ;
Cotter, David .
PROTEOMICS, 2006, 6 (11) :3414-3425
[6]   Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression [J].
Behan, A. T. ;
Byrne, C. ;
Dunn, M. J. ;
Cagney, G. ;
Cotter, D. R. .
MOLECULAR PSYCHIATRY, 2009, 14 (06) :601-613
[7]   GABAergic interneurons: Implications for understanding schizophrenia and bipolar disorder [J].
Benes, FM ;
Berretta, S .
NEUROPSYCHOPHARMACOLOGY, 2001, 25 (01) :1-27
[8]   The density of pyramidal and nonpyramidal neurons in anterior cingulate cortex of schizophrenic and bipolar subjects [J].
Benes, FM ;
Vincent, SL ;
Todtenkopf, M .
BIOLOGICAL PSYCHIATRY, 2001, 50 (06) :395-406
[10]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3