title: Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder.
abstract: OBJECTIVE
  Many studies indicate a genetic predisposition to bipolar disorder (BD) and suggest that a number of abnormal genes are involved in its development. In this study, we used DNA microarray technology to analyze gene-expression profiles in the postmortem frontal cortex of subjects with BD.
  
  
  METHODS
  Microarray hybridization was performed using human 19K microarray with universal human reference RNA in each hybridization. The reference cDNA was labelled with Cy3 and experimental cDNA, with Cy5. Glass array slides were cohybridized with equal amounts of mixed reference and experimental cDNA. Selected gene targets were further verified using real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  We found that 831 genes were differentially expressed in subjects with BD, including a number of genes in the mitochondrial electron transport chain (ETC), phosphatidylinositol-signalling system and glycolysis/ gluconeogenesis. Eight genes coding for the components of the mitochondrial ETC were identified along with 15 others related to mitochondrial function. Downregulation of NADH-ubiquinone oxidoreductase 20-kd subunit (ETC complex I), cytochrome c oxidase polypeptide Vic (ETC complex IV) and ATP synthase lipid-binding protein (ETC complex V) were further verified by real-time PCR. We also found that the expression of the NADH-ubiquinone oxidoreductase 20-kd subunit was increased in subjects with BD who were receiving mood-stabilizing treatment with lithium at the time of death, when compared with subjects with BD who were not being treated with lithium.
  
  
  CONCLUSIONS
  Because the mitochondrial ETC is a major source for the generation of reactive oxygen species, these findings suggest that oxidative damage may play an important role in the pathophysiology of BD and that neuroprotection against this damage may be involved in the effect of lithium treatment.
authors.affiliation: The Vivian Rakoff Mood Disorders Laboratory, Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Ont, Canada.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Sun
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Tseng
authors.forename: L Trevor
authors.initials: LT
authors.lastname: Young
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D004579:Electron Transport / Q000502:physiology*; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018076:DNA, Complementary; D045222:Electron Transport Chain Complex Proteins