Aberrant REST-mediated transcriptional regulation in major depressive disorder.
There is growing evidence that aberrant transcriptional regulation is one of the key components of the pathophysiology of mood disorders. The repressor element-1 silencing transcription factor (REST) is a negative regulator of genes that contain the repressor element-1 (RE-1) binding site. REST has many target genes, including corticotropin releasing hormone (CRH), brain-derived neurotrophic factor, serotonin 1A receptor, which are suggested to be involved in the pathophysiology of depression and the action of antidepressants. However, a potential role for REST-mediated transcriptional regulation in mood disorders remains unclear. In this study, we examined the mRNA levels of REST and its known and putative target genes, using quantitative real-time PCR in peripheral blood cells of patients with major depressive and bipolar disorders in both a current depressive and a remissive state. We found reduced mRNA expression of REST and increased mRNA expression of CRH, adenylate cyclase 5, and the tumor necrosis factor superfamily, member 12-13 in patients with major depressive disorder in a current depressive state, but not in a remissive state. Altered expression of these mRNAs was not found in patients with bipolar disorder. Our results suggest that the aberrant REST-mediated transcriptional regulation of, at least, CRH, adenylate cyclase 5, and tumor necrosis factor superfamily, member 12-13, might be state-dependent and associated with the pathophysiology of major depression.
Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
Koji
K
Otsuki
Shusaku
S
Uchida
Yusuke
Y
Wakabayashi
Toshio
T
Matsubara
Teruyuki
T
Hobara
Hiromasa
H
Funato
Yoshifumi
Y
Watanabe
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D000099229:RE1-Silencing Transcription Factor
D000262:Adenylyl Cyclases; D003346:Corticotropin-Releasing Hormone; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000099229:RE1-Silencing Transcription Factor; C419510:adenylyl cyclase type V