Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson's Disease
Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson's Disease
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DOI：
10.3390/molecules25112502
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发表时间：
2020-06-01
期刊：
影响因子：
4.6
通讯作者：
Toenges, Lars
中科院分区：
文献类型：
--
作者：
Ostendorf, Friederike;Metzdorf, Judith;Toenges, Lars
帕金森病（PD）是一种多因素的神经退行性疾病。近年来，一些研究表明，胃肠道系统和肠道微生物组影响中枢神经系统功能。由此触发的病理机制改变神经退行性疾病中的神经元功能，包括帕金森病中的多巴胺能神经元。在这项研究中，我们采用了一个模型系统的PD培养的原代中脑细胞，并使用农药鱼藤酮模型多巴胺能细胞损伤。我们研究了Rho激酶抑制剂法舒地尔和短链脂肪酸（SCFA）丙酸在细胞形态学测定、细胞存活、基因和蛋白质表达中对原代神经元的神经保护作用。法舒地尔应用导致多巴胺能细胞的神经炎生长显著增强和细胞存活增加。丙酸的应用主要促进多巴胺能细胞对鱼藤酮毒性的细胞存活，并在中等程度上增加神经突起的生长。有趣的是，法舒地尔增强突触素的基因表达，而丙酸显著增加酪氨酸羟化酶（TH）的基因表达水平。关于蛋白质表达，丙酸处理增加了STAT3水平，但没有导致指示途径活化的磷酸化增加。我们的研究结果表明，法舒地尔和丙酸治疗显示出有益的潜力，在鱼藤酮损伤的原代中脑细胞。
Parkinson's disease (PD) is a multifactorial neurodegenerative disease. In recent years, several studies demonstrated that the gastroenteric system and intestinal microbiome influence central nervous system function. The pathological mechanisms triggered thereby change neuronal function in neurodegenerative diseases including dopaminergic neurons in Parkinson ' s disease. In this study, we employed a model system for PD of cultured primary mesencephalic cells and used the pesticide rotenone to model dopaminergic cell damage. We examined neuroprotective effects of the Rho kinase inhibitor Fasudil and the short chain fatty acid (SCFA) propionic acid on primary neurons in cell morphological assays, cell survival, gene and protein expression. Fasudil application resulted in significantly enhanced neuritic outgrowth and increased cell survival of dopaminergic cells. The application of propionic acid primarily promoted cell survival of dopaminergic cells against rotenone toxicity and increased neurite outgrowth to a moderate extent. Interestingly, Fasudil augmented gene expression of synaptophysin whereas gene expression levels of tyrosine hydroxylase (TH) were substantially increased by propionic acid. Concerning protein expression propionic acid treatment increased STAT3 levels but did not lead to an increased phosphorylation indicative of pathway activation. Our findings indicate that both Fasudil and propionic acid treatment show beneficial potential in rotenone-lesioned primary mesencephalic cells.