MicroRNA Expression Profiling Screen miR-3557/324-Targeted CaMK/mTOR in the Rat Striatum of Parkinson's Disease in Regular Aerobic Exercise
MicroRNA Expression Profiling Screen miR-3557/324-Targeted CaMK/mTOR in the Rat Striatum of Parkinson's Disease in Regular Aerobic Exercise
复制标题
定期有氧运动中帕金森病大鼠纹状体中的 MicroRNA 表达谱筛选 miR-3557/324 靶向 CaMK/mTOR
DOI：
10.1155/2019/7654798
复制
发表时间：
2019-01-01
影响因子：
--
通讯作者：
Yin, Dazhong
中科院分区：
文献类型：
--
作者：
Liu, Wenfeng;Li, Li;Yin, Dazhong
本研究旨在筛选有规律有氧运动帕金森病(PD)大鼠模型中的靶miRNAs，并研究miR-3557/324靶向差异信号的机制。将大鼠分为安静对照组(SED-PD，n=18)和有氧运动组(ex-PD，n=22)。常规有氧运动8周后，建立6-羟基多巴胺(6-OHDA-)诱导的帕金森病损伤模型。有氧运动增强了6-OHDA诱导的帕金森病大鼠的抗损伤能力。注射盐酸阿朴吗啡后的旋转行为明显减轻。扫描电子显微镜下，纹状体神经元、轴突和绒毛排列清晰、紧密，神经元和轴突明显变大。与SED-PD组相比，前PD组酪氨酸羟化酶(TH)活性显著升高，α-突触核蛋白表达显著降低。从miRNA芯片筛选，我们进一步发现miR-3557的上调和miR-324的下调与钙调节信号通路密切相关，延缓了帕金森病有氧运动的进展。与SED-PD组相比，EX-PD组钙/钙调蛋白依赖性蛋白激酶II(CaMK2α)表达上调，而CaMKV和电压依赖性阴离子选择通道蛋白1(VDac1)表达明显下调。此外，磷脂酰肌醇-3-激酶(PI3K)/哺乳动物雷帕霉素靶标(MTOR)的表达被激活，泛素羧基末端水解酶L1(UCH-L1)的表达上调。结论：规律有氧运动延缓神经退行性疾病和损伤的适应机制是激活miR-3557/324，调节其靶点之一的CaMKs信号通路。CaMKs与mTOR通路相关基因表达相协调，使UCH-L1水平升高，有利于延缓神经退行性变或改善PD病变的发病机制。
This study aimed to screen the target miRNAs and to investigate the differential miR-3557/324-targeted signal mechanisms in the rats' model of Parkinson's disease (PD) with regular aerobic exercise. Rats were divided into sedentary control PD group (SED-PD, n = 18) and aerobic exercise PD group (EX-PD, n = 22). After 8 weeks of regular aerobic exercise, a 6-hydroxydopamine- (6-OHDA-) induced PD lesion model was constructed. Preregular aerobic exercises enhanced the injury resistance of rats with 6-OHDA-induced PD. The rotational behavior after injection of apomorphine hydrochloride was alleviated. Under the scanning electron microscopy, we found the neurons, axons, and villi of the striatum were clearly and tightly arranged, and neurons and axons significantly becoming larger. Tyrosine hydroxylase (TH) was increased significantly and α-synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group. Screening from miRNA microarray chip, we further found upregulation of miR-3557 and downregulation of miR-324 were closely related to the calcium-modulating signaling pathway, remitting the progress of Parkinson's disease on aerobic exercise. Compared to the SED-PD group, Ca2+/calmodulin dependent protein kinase II (CaMK2α) was upregulated, but CaMKV and voltage-dependent anion-selective channel protein 1 (Vdac1) were significantly downregulated in the EX-PD group. Additionally, phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) expression were activated, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) expression was upregulated in the EX-PD group. Conclusions: the adaptive mechanism of regular aerobic exercise delaying neurodegenerative diseases and lesions was that miR-3557/324 was activated to regulate one of its targets CaMKs signaling pathways. CaMKs, coordinated with mTOR pathway-related gene expression, improved UCH-L1 level to favor for delaying neurodegeneration or improving the pathogenesis of PD lesions.