Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Department of Psychiatry, Pomeranian University of Medicine, Szczecin, Poland.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt A):28-33. doi: 10.1016/j.pnpbp.2017.06.013. Epub 2017 Jun 16.
We investigated the effect of long-term lithium treatment on very-small embryonic-like stem cells (VSELs) and the mRNA expression of pluripotency and glial markers, in peripheral blood, in patients with bipolar disorder (BD).
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 8-40years (mean 16years) and 15 control subjects (aged 50±5years) were included. The number of VSELs was measured by flow cytometric analysis. Assessment of the mRNA levels of pluripotency markers (Oct-4, Sox 2 and Nanog) and glial markers (glial fibrillary acidic protein - GFAP, Olig1 and Olig2) was performed, using the Real-time quantitative reverse transcription PCR.
In BD patients not taking lithium, the number of VSELs was significantly higher than in control subjects and correlated with the duration of illness. The expression of pluripotency markers was significantly higher than in the controls and correlated with the number of VSELs. The mRNA levels of the Olig1 and Olig 2 were higher than in the controls and those of the GFAP were higher than in patients receiving lithium. In lithium-treated BD patients the number of VSELs was similar to controls and correlated negatively with the duration of lithium treatment and serum lithium concentration. The mRNA levels of Oct-4, Sox-2, GFAP and Olig1 were not different from controls. The mRNA expression of Nanog was significantly higher and correlated with the number of VSELs. The mRNA expression of Olig 2 was higher than in the BD patients not taking lithium.
Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress. The higher expression of peripheral mRNA markers in BD patients may involve ongoing inflammatory process, compensatory mechanisms and regenerative responses. Long-term lithium treatment may attenuate these mechanisms, especially in relation to the transcription factors Oct-4, Sox-2, GFAP and Olig1.
我们研究了长期锂治疗对小胚胎样干细胞（VSELs）和多能性及神经胶质标记物的 mRNA 表达的影响，这些标记物存在于外周血中的双相障碍（BD）患者中。
纳入 15 名未接受锂治疗、病程>10 年的 BD 患者（年龄 53±7 岁），15 名接受锂治疗 8-40 年（平均 16 年）的 BD 患者和 15 名对照者（年龄 50±5 岁）。通过流式细胞术分析测量 VSELs 的数量。采用实时定量逆转录 PCR 检测多能性标记物（Oct-4、Sox2 和 Nanog）和神经胶质标记物（胶质纤维酸性蛋白-GFAP、Olig1 和 Olig2）的 mRNA 水平。
未接受锂治疗的 BD 患者的 VSELs 数量明显高于对照组，且与病程相关。多能性标记物的表达明显高于对照组，并与 VSELs 的数量相关。Olig1 和 Olig2 的 mRNA 水平高于对照组，GFAP 的 mRNA 水平高于锂治疗的 BD 患者。锂治疗的 BD 患者的 VSELs 数量与对照组相似，与锂治疗的持续时间和血清锂浓度呈负相关。Oct-4、Sox-2、GFAP 和 Olig1 的 mRNA 水平与对照组无差异。Nanog 的 mRNA 表达明显升高，与 VSELs 的数量相关。Olig 2 的 mRNA 表达高于未接受锂治疗的 BD 患者。
长期锂治疗可能通过减少外周血循环中的 VSELs 数量来抑制再生过程的激活。这些细胞在未接受锂治疗的 BD 患者中可能提供疾病及其临床进展的新的潜在生物学标志物。BD 患者外周血中 mRNA 标记物的高表达可能涉及持续的炎症过程、代偿机制和再生反应。长期锂治疗可能会减弱这些机制，特别是与转录因子 Oct-4、Sox-2、GFAP 和 Olig1 有关。
