Gene expression differences in bipolar disorder revealed by cDNA array analysis of post-mortem frontal cortex.
Previous studies have implicated a number of biochemical pathways in the etiology of bipolar disorder (BD). However, the precise abnormalities underlying this disorder remain to be established. To investigate novel factors that may be important in the pathophysiology of BD, we utilized cDNA expression arrays to examine differences in expression of up to 1200 genes known to be involved in potentially relevant biochemical processes. This investigation was undertaken in post-mortem samples of frontal cortex tissue from patients with BD and matched controls, obtained (n = 10/group) from the Stanley Foundation Neuropathology Consortium. Results include significant (greater than 35% change in signal intensity) differences between BD and controls in a number of genes (n = 24). Selected targets were analyzed by RT-PCR, which confirmed a decrease in transforming growth factor-beta1 (TGF-beta 1), and an increase in both caspase-8 precursor (casp-8) and transducer of erbB2 (Tob) expression in BD. We further observed a significant decrease of TGF-beta 1 mRNA levels in BD by RT-PCR in individual post-mortem samples. Given the neuroprotective role attributed to this inhibitory cytokine, our results suggest that the down-regulation of TGF-beta 1 may lead to various neurotoxic insults potentially involved in the etiology of certain mood disorders.
Bezchlibnyk
Y B
YB
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Wang
J F
JF
McQueen
G M
GM
Young
L T
LT
D000328:Adult; D000367:Age Factors; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C098669:TOB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases