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多巴胺能神经元移植和褪黑素联合给药对帕金森病氧化应激诱导细胞死亡的影响。

The effect of dopaminergic neuron transplantation and melatonin co-administration on oxidative stress-induced cell death in Parkinson's disease.

机构信息

Anatomy Department, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Anatomy and Biology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Metab Brain Dis. 2022 Dec;37(8):2677-2685. doi: 10.1007/s11011-022-01021-5. Epub 2022 Sep 8.

Abstract

A gradual degeneration of the striatum and loss of nigral dopamine cells are characteristic of Parkinson's disease. Nowadays, combination therapy for neurodegenerative disease is considered. This study aimed to investigate the effects of melatonin and dopaminergic neurons derived from adipose tissue stem cells (ADSCs) in a rat model of Parkinson's disease. Parkinson's disease was induced in rats using neurotoxin 6-Hydroxydopamine. The treatment was performed using melatonin and dopaminergic neurons transplantation. Subsequently, behavioral tests, western blot analysis for Caspase-3 expression, GSH (Glutathione) content and stereology analysis for the volume and cell number of substantia nigra and striatum were performed. Treatment with melatonin and dopaminergic neuron transplantation increased the number of neurons in substantia nigra and striatum while the number of glial cell and the volume of substantia nigra and striatum did not show significant change between groups. Western blot analysis for caspase 3 indicated the significant differences between groups. The results also indicated the increased level of glutathione (GSH) content in treatment groups. this study showed that combination therapy with melatonin and dopaminergic neurons could greatly protect the neurons, reduce oxidative stress and improve the symptoms of PD.

摘要

纹状体的逐渐退化和黑质多巴胺细胞的丧失是帕金森病的特征。如今,人们认为联合治疗神经退行性疾病是可行的。本研究旨在探讨褪黑素和脂肪组织干细胞(ADSCs)衍生的多巴胺能神经元在帕金森病大鼠模型中的作用。使用神经毒素 6-羟多巴胺诱导大鼠帕金森病。采用褪黑素和多巴胺能神经元移植进行治疗。随后进行行为测试、Caspase-3 表达的 Western blot 分析、GSH(谷胱甘肽)含量和黑质和纹状体体积和细胞数的立体学分析。褪黑素和多巴胺能神经元移植治疗增加了黑质和纹状体神经元的数量,而神经胶质细胞的数量和黑质和纹状体的体积在各组之间没有显示出显著的变化。Caspase 3 的 Western blot 分析表明组间存在显著差异。结果还表明治疗组的谷胱甘肽(GSH)含量增加。本研究表明,褪黑素和多巴胺能神经元联合治疗可以很好地保护神经元,减轻氧化应激,改善 PD 症状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87a/9668958/de157da70847/11011_2022_1021_Fig1_HTML.jpg

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