Gene expression profiling in Brodmann's area 46 from subjects with schizophrenia.
OBJECTIVE
To identify altered gene expression in the dorsolateral prefrontal cortex obtained after death from subjects with schizophrenia.


METHODS
Restriction fragment differential display (RFDD) was used to measure levels of mRNA in Brodmann area (BA) 46 from schizophrenia and control subjects. Findings on specific mRNA identified with RFDD were further investigated using real-time polymerase chain reaction (real-time PCR), PCR and western blotting.


RESULTS
Levels of mRNA for 63 of approximately 12,500 genes differed in BA 46 in schizophrenia. Subsequent real-time PCR has shown that mRNA for muscleblind protein 1 (MBNL1) and protocadherin 17 (PCDH17) are increased in BA 46 from subjects with schizophrenia of short, but not long, duration. Altered levels of mRNA for neither gene were present in BA 9 from subjects with schizophrenia or in either cortical area from subjects with bipolar 1 disorder. By contrast, both RFDD and real-time PCR failed to show altered expression of the schizophrenia candidate gene disrupted in schizophrenia 1 (DISC1) BA46 from any diagnostic cohort.


CONCLUSIONS
The present study has identified genes that are differentially expressed in BA 46 in schizophrenia. Initial studies have shown that there is a need for a careful validation of genes shown to be affected in schizophrenia using high-throughput technologies. In addition the present study has shown that gene expression may vary considerably depending on the duration of schizophrenia. This raises the hypothesis that changing gene expression may be underlying the change in symptom profile that occurs with disease progression in some subjects with schizophrenia.
Dean
Brian
B
Rebecca L. Cooper Research Laboratories, Mental Health Research Institute of Victoria, Locked Bag 11, Parkville, Vic. 3052, Australia. bdean_mhri@iprimus.com.au
Keriakous
Dahlia
D
Scarr
Elizabeth
E
Thomas
Elizabeth A
EA
D000328:Adult; D000818:Animals; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction
C412476:DISC1 protein, human; D018076:DNA, Complementary; C493663:MBNL1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins