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Liposomal Form of L-Dopa and SH-Sy5y Cell-Derived Exosomes Modulate the Tyrosine Hydroxylase/Dopamine Receptor D2 Signaling Pathway in Parkinson's Rat Models
Journal of Molecular Neuroscience ( IF 3.1 ) Pub Date : 2021-06-14 , DOI: 10.1007/s12031-021-01853-3
Parastoo Zarrin 1 , Mahmood Dehghani Ashkezari 1 , Seyed Morteza Seifati 1
Affiliation  

Parkinson's disease is a progressive neurodegenerative disorder in which dopaminergic neurons located in the substantia nigra are gradually lost. Currently, combined treatment strategies are receiving increasing attention as potential therapeutic approaches for Parkinson's disease. This study aimed to evaluate the potential effects of exosomes released from SH-Sy5y cells and the liposomal form of L-dopa on Parkinson's rat models. Twenty-five male Wistar albino rats, in five groups, were included in this study. Parkinson's disease was induced through microinjection of 6-OHDA (2.5 mg/mL) into the right substantia nigra. The exosomes released from the SH-Sy5y cell line were isolated and administered (0.2 µg/5 µL) alone or in combination with the liposomal form of L-Dopa (80 mg/kg) to the defined model groups. Behavioral tests and molecular assays were conducted to evaluate the expression levels of tyrosine hydroxylase (TH) and dopamine receptor D2 (DRD2). The rats in the groups receiving the combined liposomal form of L-Dopa and exosome treatment and the liposomal form of L-Dopa alone showed a significant improvement in their movement ability (p < 0.05). At molecular levels, these two groups also exhibited significant increases in Th (0.005 ± 0.001) and Drd2 (0.002 ± 0.0001) expression compared to controls (p < 0.05). The observed alterations of Th and Drd2 expression were not statistically significant in exosome- and L-Dopa-treated groups. The current study shows that exosome-derived neuronal cells and liposomal form of L-Dopa can protect different cells against pathological complications such as Parkinson’s disease.



中文翻译:

L-多巴和 SH-Sy5y 细胞衍生外泌体的脂质体形式调节帕金森大鼠模型中的酪氨酸羟化酶/多巴胺受体 D2 信号通路

帕金森病是一种进行性神经退行性疾病,其中位于黑质的多巴胺能神经元逐渐丧失。目前,联合治疗策略作为帕金森病的潜在治疗方法正受到越来越多的关注。本研究旨在评估从 SH-Sy5y 细胞释放的外泌体和左旋多巴脂质体形式对帕金森大鼠模型的潜在影响。本研究包括五组 25 只雄性 Wistar 白化病大鼠。通过将 6-OHDA (2.5 mg/mL) 显微注射到右侧黑质中诱发帕金森病。分离从 SH-Sy5y 细胞系释放的外泌体,单独或与脂质体形式的左旋多巴 (80 mg/kg) 联合给药 (0.2 µg/5 µL) 到定义的模型组。进行行为测试和分子测定以评估酪氨酸羟化酶 (TH) 和多巴胺受体 D2 (DRD2) 的表达水平。左旋多巴脂质体联合外泌体治疗组和左旋多巴脂质体单独治疗组大鼠的运动能力显着提高。p  < 0.05)。在分子水平上,与对照组相比,这两组的Th (0.005 ± 0.001) 和Drd2 (0.002 ± 0.0001) 表达也显着增加 ( p  < 0.05)。在外泌体和左旋多巴治疗组中观察到的ThDrd2表达变化没有统计学意义。目前的研究表明,外泌体衍生的神经元细胞和脂质体形式的左旋多巴可以保护不同的细胞免受帕金森病等病理并发症的影响。

更新日期:2021-06-14
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