Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia.
Schizophrenia is likely to be a consequence of serial alterations in a number of genes that, together with environmental factors, will lead to the establishment of the illness. The dorsolateral prefrontal cortex (Brodmann's Area 46) is implicated in schizophrenia and executes high functions such as working memory, differentiation of conflicting thoughts, determination of right and wrong concepts, correct social behavior and personality expression. We performed a comparative proteome analysis using two-dimensional gel electrophoresis of pools from 9 schizophrenia and 7 healthy control patients' dorsolateral prefrontal cortex aiming to identify, by mass spectrometry, alterations in protein expression that could be related to the disease. In schizophrenia-derived samples, our analysis revealed 10 downregulated and 14 upregulated proteins. These included alterations previously implicated in schizophrenia, such as oligodendrocyte-related proteins (myelin basic protein and transferrin), as well as malate dehydrogenase, aconitase, ATP synthase subunits and cytoskeleton-related proteins. Also, six new putative disease markers were identified, including energy metabolism, cytoskeleton and cell signaling proteins. Our data not only reinforces the involvement of proteins previously implicated in schizophrenia, but also suggests new markers, providing further information to foster the comprehension of this important disease.
Martins-de-Souza
Daniel
D
Laboratório de Neurociências, Instituto de Psiquiatria, Faculdade de Medicina da USP, Rua Dr. Ovídio Pires de Campos, SP, Brazil. martins@mpipsykl.mpg.de
Gattaz
Wagner F
WF
Schmitt
Andrea
A
Maccarrone
Giuseppina
G
Hunyadi-Gulyás
Eva
E
Eberlin
Marcos N
MN
Souza
Gustavo H M F
GH
Marangoni
Sérgio
S
Novello
José C
JC
Turck
Christoph W
CW
Dias-Neto
Emmanuel
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009836:Oligodendroglia / Q000378:metabolism*; D010449:Peptide Mapping / Q000379:methods; D017397:Prefrontal Cortex / Q000378:metabolism*; D040901:Proteomics; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D053719:Tandem Mass Spectrometry / Q000379:methods
D015415:Biomarkers