Engrafted primary type-2 astrocytes improve the recovery of the nigrostriatal pathway in a rat model of Parkinson's disease
Engrafted primary type-2 astrocytes improve the recovery of the nigrostriatal pathway in a rat model of Parkinson's disease
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DOI：
10.1007/s11010-020-03931-3
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发表时间：
2020-10
影响因子：
4.3
通讯作者：
Yanyun Sun;Xiao-jun Lu;Xinghui Fu;Ye Zhang;Yan Zhan;Jia-Bin Liu;Lingxia Zhao;Chunlin Xia
中科院分区：
文献类型：
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作者：
Yanyun Sun;Xiao-jun Lu;Xinghui Fu;Ye Zhang;Yan Zhan;Jia-Bin Liu;Lingxia Zhao;Chunlin Xia
帕金森病（PD）是一种以黑质中多巴胺能神经元的进行性丧失和纹状体中神经递质多巴胺的耗竭为特征的疾病。我们发表的研究结果表明，在PD的进展过程中，束状和伸长蛋白zeta-1 （FEZ1）在星形胶质细胞介导的多巴胺神经元保护和神经元微环境调节中发挥作用。本研究探讨了植入高表达FEZ1的2型星形细胞（T2As）对PD大鼠症状改善和功能重建的影响。将T2As立体定向移植到6-羟多巴胺（6-OHDA）诱导的PD大鼠纹状体中。通过阿波啡（APO）诱导的旋转检查来评估多巴胺神经元损伤和运动功能。值得注意的是，移植细胞在病变环境中存活了6周或更长时间。此外，在旋转行为测试中，T2As移植降低了apo诱导的旋转的平均速度和持续时间，并增加了驱动时间。在黑质中，T2As移植降低了pd诱导的GFAP、TH和FEZ1下调。移植细胞只迁移到纹状体注射部位附近的其他区域，并分化为GFAP+星形胶质细胞或TH+神经元。此外，通过高效液相色谱检测单胺类神经递质，我们发现黑质纹状体通路得到了一定程度的修复。综上所述，植入高表达FEZ1的T2As可改善PD大鼠的症状和功能重建，为FEZ1作为潜在靶点和植入T2As作为治疗PD的治疗策略提供了理论依据。
Parkinson’s disease (PD) is a disorder characterized by a progressive loss of the dopaminergic neurons in the substantia nigra and a depletion of the neurotransmitter dopamine in the striatum. Our published results indicate that fasciculation and elongation protein zeta-1 (FEZ1) plays a role in the astrocyte-mediated protection of dopamine neurons and regulation of the neuronal microenvironment during the progression of PD. In this study, we examined the effects of engrafted type-2 astrocytes (T2As) with high expression of FEZ1 on the improvement of the symptoms and functional reconstruction of PD rats. T2As were stereotactically transplanted into the striatum of rats with PD induced by 6-hydroxydopamine (6-OHDA). An examination of apomorphine (APO)-induced rotations was performed to evaluate dopamine neuron damage and motor functions. Remarkably, the grafted cells survived in the lesion environment for six weeks or longer after implantation. In addition, the transplantation of T2As decrease the average velocity and the duration time of the APO-induced rotations, and increase the actuation time, as measured in the rotation behavioural tests. In the substantia nigra, the transplantation of T2As reduced the PD-induced GFAP, TH and FEZ1 downregulation. The grafted cells exclusively migrated to other regions near the injection site in the striatum and differentiated into GFAP+astrocytes or TH+neurons. Furthermore, by detecting monoamine neurotransmitters through high-performance liquid chromatography, we found that the nigrostriatal pathway had been repaired to some extent. Taken together, these results suggest that engrafted T2As with high expression of FEZ1 improved the symptoms and functional reconstruction of PD rats, providing a theoretical basis for FEZ1 as a potential target and engraftment of T2As as a therapeutic strategy in the treatment of PD.