Wnt1 Promotes EAAT2 Expression and Mediates the Protective Effects of Astrocytes on Dopaminergic Cells in Parkinson’s Disease

作者：Lei Wei, Chuan Chen, Li Ding, Mingshu Mo, Jing Zou, Zhenze Lu, Haiyan Li, Haotian Wu, Yongqiang Dai, Pingyi Xu, Zhengqi Lu · 发表于：Neural Plasticity · 年份：2019 · DOI：10.1155/2019/1247276 · 被引用次数：30 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Nuclear Receptors and Signaling、Nerve injury and regeneration

Background . Wnt/ β -catenin signaling has been reported to exert cytoprotective effects in a cellular model of Parkinson’s disease (PD). Glutamate excitotoxicity has been suggested to contribute to the pathogenesis of PD, and excitatory amino acid transporters (EAATs) play a predominant role in clearing excessive glutamate. EAAT2 is mainly expressed in astrocytes, which are an important source of Wnt signaling in the brain. Methods . Wnt1-overexpressing U251 astrocytes were indirectly cocultured with dopaminergic SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Cell toxicity was determined by cell viability and flow cytometric detection. Glutamate level in the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the expression of Wnt1, β -catenin, and EAAT2. Immunofluorescence was used to display the expression and translocation of NF- κ B p65. Results . 6-OHDA treatment significantly decreased cell viability in both U251 cells and SH-SY5Y cells, inhibited the expression of Wnt1, β -catenin, and EAAT2 in U251 cells, and increased the glutamate level in the culture medium. Coculture with Wnt1-overexpressing U251 cells attenuated 6-OHDA-induced apoptosis in SH-SY5Y cells. Overexpression of Wnt1 decreased the glutamate level in the culture media, upregulated β -catenin, EAAT2, and NF- κ B levels, and promoted the translocation of NF- κ B from the cytoplasm to the nucleus in U251 cells. Conclusion . Wnt1 promo...