Ferensztajn-Rochowiak Ewa, Tarnowski Maciej, Samochowiec Jerzy, Michalak Michal, Ratajczak Mariusz Z, Rybakowski Janusz K
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland.
Department of Physiology, Pomeranian University of Medicine, Szczecin, Poland.
Pharmacol Rep. 2016 Oct;68(5):1042-5. doi: 10.1016/j.pharep.2016.06.006. Epub 2016 Jul 26.
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.
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.
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.
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.
目的是评估双相情感障碍（BD）患者中多能性主要转录因子如八聚体结合转录因子4（Oct4）、性别决定区Y盒2（Sox2）和同源盒蛋白Nanog的外周mRNA表达，以及长期锂盐治疗的效果。
纳入15例未接受锂盐治疗、病程>10年的BD患者（年龄53±7岁），15例接受锂盐治疗8 - 40年（平均16年）的BD患者（年龄55±6岁）和15例对照者（年龄50±5岁）。采用实时定量逆转录PCR（RQ-PCR）方法评估多能性标志物（Oct-4、Sox 2和Nanog）的mRNA水平，并通过流式细胞术分析测量CD34 + 非常小的胚胎样干细胞（VSELs）的数量。
在未接受锂盐治疗的BD患者中，所有三个多能性基因的表达均显著高于对照者。在该组中，Oct-4、Sox2和Nanog也与CD34 + VSELs/μl的数量呈正相关。在接受锂盐治疗的患者中，Nanog的mRNA水平显著高于对照个体，并与CD34 + VSELs的数量和百分比相关。
未接受锂盐治疗且病程较长的BD患者中多能性主要转录因子的过表达可能有助于疾病的发病机制，并使其成为BD的潜在生物学标志物。长期锂盐治疗可能会减弱这些过度的再生过程，尤其是与转录因子Oct-4和Sox2相关的过程。
