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New insights on Parkinson's disease from differentiation of SH-SY5Y into dopaminergic neurons: An involvement of aquaporin4 and 9
Molecular and Cellular Neuroscience ( IF 2.6 ) Pub Date : 2018-02-08 , DOI: 10.1016/j.mcn.2018.02.006
Rosanna Avola , Adriana Carol Eleonora Graziano , Giovanna Pannuzzo , Ferdaous Albouchi , Venera Cardile

The purpose of this research was to explore the behavior of aquaporins (AQPs) in an in vitro model of Parkinson's disease that is a recurrent neurodegenerative disorder caused by the gradual, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Because of postmortem studies have provided evidences for oxidative damage and alteration of water flow and energy metabolism, we carried out an investigation about AQP4 and 9, demonstrated in the brain to maintain water and energy homeostasis. As an appropriate in vitro cell model, we used SH-SY5Y cultures and induced their differentiation into a mature dopaminergic neuron phenotype with retinoic acid (RA) alone or in association with phorbol-12-myristate-13-acetate (MPA). The association RA plus MPA provided the most complete and mature neuron phenotype, as demonstrated by high levels of β-Tubulin III, MAP-2, and tyrosine hydroxylase. After validation of cell differentiation, the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and H2O2 were applied to reproduce a Parkinson's-like stress. The results confirmed RA/MPA differentiated SH-SY5Y as a useful in vitro system for studying neurotoxicity and for using in a MPTP and H2O2-induced Parkinson's disease cell model. Moreover, the data demonstrated that neuronal differentiation, neurotoxicity, neuroinflammation, and oxidative stress are strongly correlated with dynamic changes of AQP4 and 9 transcription and transduction. New in vitro and in vivo experiments are needed to confirm these innovative outcomes.



中文翻译:

从SH-SY5Y分化为多巴胺能神经元对帕金森氏病的新见解:水通道蛋白4和9的参与

这项研究的目的是探讨帕金森氏病体外模型中水通道蛋白(AQPs)的行为,帕金森氏病是由黑质致密部中多巴胺能神经元逐渐,进行性丧失引起的复发性神经退行性疾病。由于事后研究为氧化损伤以及水流量和能量代谢的改变提供了证据,因此我们对AQP4和9进行了研究,证明了AQP4和9在大脑中可以维持水和能量的动态平衡。作为合适的体外细胞模型中,我们使用SH-SY5Y培养物,并单独使用视黄酸(RA)或与phorbol-12-肉豆蔻酸酯13-乙酸酯(MPA)结合诱导分化为成熟的多巴胺能神经元表型。RA与MPA的关联提供了最完整和最成熟的神经元表型,如高水平的β-微管蛋白III,MAP-2和酪氨酸羟化酶所证明的。在确认细胞分化后,应用神经毒素1-甲基-4-苯基-1、2、3、6-四氢吡啶(MPTP)和H 2 O 2来重现帕金森氏样应激。结果证实RA / MPA分化的SH-SY5Y是研究神经毒性以及用于MPTP和H 2 O 2的有用的体外系统。诱发的帕金森氏病细胞模型。此外,数据表明神经元分化,神经毒性,神经炎症和氧化应激与AQP4和9转录和转导的动态变化密切相关。需要新的体外体内实验来确认这些创新成果。

更新日期:2018-02-08
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