Toutouna Louiza, Nikolakopoulou Polyxeni, Poser Steven W, Masjkur Jimmy, Arps-Forker Carina, Troullinaki Maria, Grossklaus Sylvia, Bosak Viktoria, Friedrich Ulrike, Ziemssen Tjalf, Bornstein Stefan R, Chavakis Triantafyllos, Androutsellis-Theotokis Andreas
Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
Technische Universität Dresden, Department of Clinical Pathobiochemistry, Dresden 01307, Germany.
Brain Res. 2016 Jul 1;1642:124-130. doi: 10.1016/j.brainres.2016.03.014. Epub 2016 Mar 25.
Hes3 is a component of the STAT3-Ser/Hes3 Signaling Axis controlling the growth and survival of neural stem cells and other plastic cells. Pharmacological activation of this pathway promotes neuronal rescue and behavioral recovery in models of ischemic stroke and Parkinson's disease. Here we provide initial observations implicating Hes3 in the cuprizone model of demyelination and remyelination. We focus on the subpial motor cortex of mice because we detected high Hes3 expression. This area is of interest as it is impacted both in human demyelinating diseases and in the cuprizone model. We report that Hes3 expression is reduced at peak demyelination and is partially restored within 1 week after cuprizone withdrawal. This raises the possibility of Hes3 involvement in demyelination/remyelination that may warrant additional research. Supporting a possible role of Hes3 in the maintenance of oligodendrocyte markers, a Hes3 null mouse strain shows lower levels of myelin basic protein in undamaged adult mice, compared to wild-type controls. We also present a novel method for culturing the established oligodendrocyte progenitor cell line oli-neu in a manner that maintains Hes3 expression as well as its self-renewal and differentiation potential, offering an experimental tool to study Hes3. Based upon this approach, we identify a Janus kinase inhibitor and dbcAMP as powerful inducers of Hes3 gene expression. We provide a new biomarker and cell culture method that may be of interest in demyelination/remyelination research.
Hes3是STAT3-丝氨酸/Hes3信号轴的一个组成部分，该信号轴控制神经干细胞和其他可塑性细胞的生长与存活。在缺血性中风和帕金森病模型中，该信号通路的药理学激活可促进神经元修复和行为恢复。在此，我们提供了初步观察结果，表明Hes3参与脱髓鞘和髓鞘再生的铜螯合剂模型。我们将重点放在小鼠软膜下运动皮层，因为我们检测到该区域Hes3表达较高。这个区域之所以受到关注，是因为它在人类脱髓鞘疾病和铜螯合剂模型中均会受到影响。我们报告称，在脱髓鞘高峰期Hes3表达降低，在停用铜螯合剂后1周内部分恢复。这增加了Hes3参与脱髓鞘/髓鞘再生的可能性，可能值得进一步研究。支持Hes3在维持少突胶质细胞标志物方面可能发挥作用的是，与野生型对照相比，Hes3基因敲除小鼠品系在未受损的成年小鼠中髓鞘碱性蛋白水平较低。我们还提出了一种培养已建立的少突胶质细胞祖细胞系oli-neu的新方法，该方法能够维持Hes3表达及其自我更新和分化潜能，为研究Hes3提供了一种实验工具。基于这种方法，我们确定了一种janus激酶抑制剂和dbcAMP是Hes3基因表达的强力诱导剂。我们提供了一种新的生物标志物和细胞培养方法，可能对脱髓鞘/髓鞘再生研究具有重要意义。
