Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Copenhagen, Denmark; Aarhus University, Department of Biomedicine, Ole Worms Allé 3, Building 1171, DK-8000 Aarhus, Denmark; Aarhus University, Department of Molecular Biology and Genetics, Gustav Wieds Vej 10, Building 3135, DK-8000 Aarhus, Denmark.
Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2774-87. doi: 10.1016/j.neubiorev.2013.09.013. Epub 2013 Oct 1.
Modeling neurological disorders using zebrafish increases rapidly as this model system allows easy access to all developmental stages and imaging of pathological processes. A surprising degree of functional conservation has been demonstrated between human genes implicated in neurodegenerative diseases and their zebrafish orthologues. Zebrafish offers rapid high throughput screening of therapeutic compounds and live imaging of pathogenic mechanisms in vivo. Several recent zebrafish studies functionally assessed the role of the sodium-potassium pump (Na(+)/K(+)-ATPase). The Na(+)/K(+)-ATPase maintains the electrochemical gradients across the plasma membrane, essential for e.g. signaling, secondary active transport, glutamate re-uptake and neuron excitability in animal cells. Na(+)/K(+)-ATPase mutations are associated with neurological disorders, where mutations in the Na(+)/K(+)-ATPase α2 and α3 isoforms cause Familial hemiplegic migraine type 2 (FHM2) and Rapid-onset dystonia-parkinsonism (RDP)/Alternating hemiplegic childhood (AHC), respectively. In zebrafish, knock-down of Na(+)/K(+)-ATPase isoforms included skeletal and heart muscle defects, impaired embryonic motility, depolarized Rohon-beard neurons and abrupt brain ventricle development. In this review, we discuss zebrafish as a model to assess Na(+)/K(+)-ATPase isoform functions. Furthermore, studies investigating proteomic changes in both α2- and α3-isoform deficient embryos and their potential connections to the Na(+)/K(+)-ATPase functions will be discussed.
利用斑马鱼模型来研究神经紊乱的方法得到了快速发展，因为这种模型系统允许人们方便地研究所有发育阶段，并能对病理过程进行成像。在与神经退行性疾病相关的人类基因与其斑马鱼同源基因之间，已经证明存在着令人惊讶的功能保守性。斑马鱼为治疗化合物的高通量筛选提供了便利，并能在体内对致病机制进行实时成像。最近的一些斑马鱼研究对钠钾泵（Na(+)/K(+)-ATPase）的功能进行了评估。Na(+)/K(+)-ATPase 维持着质膜两侧的电化学梯度，这对动物细胞中的信号转导、次级主动转运、谷氨酸再摄取和神经元兴奋性等过程至关重要。Na(+)/K(+)-ATPase 的突变与神经紊乱有关，其中 Na(+)/K(+)-ATPase α2 和 α3 同工型的突变分别导致家族性偏瘫偏头痛 2 型（FHM2）和快速进展性肌张力障碍帕金森病（RDP）/交替性偏瘫儿童（AHC）。在斑马鱼中，Na(+)/K(+)-ATPase 同工型的敲低导致骨骼肌和心肌缺陷、胚胎运动能力受损、Rohon-beard 神经元去极化以及脑室内发育突然停止。在这篇综述中，我们讨论了斑马鱼作为一种评估 Na(+)/K(+)-ATPase 同工型功能的模型。此外，还将讨论研究 α2-和 α3-同工型缺失胚胎中的蛋白质组变化及其与 Na(+)/K(+)-ATPase 功能的潜在联系。
