2-D DIGE analysis implicates cytoskeletal abnormalities in psychiatric disease.
The mechanisms underlying white matter changes in psychiatric disease are not known. We aimed to characterise the differential protein expression in deep white matter from the dorsolateral prefrontal cortex from 35 schizophrenia, 35 bipolar disorder, and 35 control subjects, from the Stanley Array Collection. We used 2-D DIGE to profile for protein expression changes in the brain. We found 70 protein spots to be significantly differentially expressed between disease and control subjects (ANCOVA, p<0.05), 46 of which were subsequently identified by LC-MS/MS. The proteins identified included novel disease candidates as well as proteins that have previously been reported as abnormal in schizophrenia, thus reinforcing their association with the disease. Furthermore, we confirmed the direction of change for three proteins using ELISA, namely neurofilament-light, amphiphysin II, and Rab-GDP-alpha, in a subset of the Stanley Array Collection. In addition, altered expression of neurofilament-light, amphiphysin II, and Rab-GDP-alpha was not observed in the cortex of mice chronically treated with haloperidol, making it less likely that these alterations are a consequence of neuroleptic medication. The data presented here strongly suggest disruption of the cytoskeleton and its associated signal transduction proteins in schizophrenia, and to a lesser extent in bipolar disorder.
English
Jane A
JA
Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland. jane.english@ucd.ie
Dicker
Patrick
P
Föcking
Melanie
M
Dunn
Michael J
MJ
Cotter
David R
DR
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020543:Proteome / Q000187:drug effects / Q000378:metabolism*; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000378:metabolism*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D020543:Proteome; D006220:Haloperidol