title: Peripheral mRNA expression of pluripotency markers in bipolar disorder and the effect of long-term lithium treatment.
abstract: BACKGROUND
  The aim was to evaluate the peripheral mRNA expression of pluripotency master transcriptional factors such as octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2) and homeobox protein Nanog, in patients with bipolar disorder (BD), and the effect of long-term lithium treatment.
  
  
  METHODS
  Fifteen BD patients (aged 53±7years) not treated with lithium, with duration of illness>10years, 15 BD patients (aged 55±6years) treated with lithium for 8-40 years (mean 16years) and 15 control subjects (aged 50±5years) were included. Assessment of the mRNA levels of pluripotency markers (Oct-4, Sox 2 and Nanog) was performed, using the Real-time quantitative reverse transcription PCR (RQ-PCR) procedure, and the number of CD34+ very small embryonic-like stem cells (VSELs) was measured by flow cytometric analysis.
  
  
  RESULTS
  In those BD patients not treated with lithium the expression of all three pluripotency genes was significantly higher than that in the control subjects. Oct-4, Sox2 and Nanog also positively correlated with the number of CD34+ VSELs/[ul] in this group. In the lithium-treated patients the mRNA levels of Nanog were significantly higher than in the control individuals and correlated with the number and % of CD34+ VSELs.
  
  
  CONCLUSIONS
  The overexpression of the pluripotency master transcriptional factors in patients with a long duration of BD not treated with lithium, may contribute to the pathogenesis of the illness and make them potential biological markers of BD. Long-term lithium treatment may attenuate these excessive regenerative processes, especially in relation to the transcription factors Oct-4 and Sox2.
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Ferensztajn-Rochowiak
authors.affiliation: Department of Physiology, Pomeranian University of Medicine, Szczecin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Tarnowski
authors.affiliation: Department of Psychiatry, Pomeranian University of Medicine, Szczecin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Samochowiec
authors.affiliation: Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Department of Physiology, Pomeranian University of Medicine, Szczecin, Poland; Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.affiliation: Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: janusz.rybakowski@gmail.com.
authors.forename: Janusz K
authors.initials: JK
authors.lastname: Rybakowski
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D008094:Lithium
keywords: Nanog; Oct-4; Sox 2; bipolar disorder; lithium