Adulthood Exposure to Lipopolysaccharide Exacerbates the Neurotoxic and Inflammatory Effects of Rotenone in the Substantia Nigra.
Adulthood Exposure to Lipopolysaccharide Exacerbates the Neurotoxic and Inflammatory Effects of Rotenone in the Substantia Nigra.
复制标题
成年期接触脂多糖会加剧黑质中鱼藤酮的神经毒性和炎症作用
DOI：
10.3389/fnmol.2017.00131
复制
发表时间：
2017
影响因子：
4.8
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Huang C;Zhu L;Li H;Shi FG;Wang GQ;Wei YZ;Liu J;Zhang F
帕金森病（PD）是第二大神经退行性疾病，其特征是黑质（SN）中多巴胺（DA）神经元的区域性减少。尽管进行了深入的研究，PD进展过程的病因仍不清楚。本研究旨在探讨脂多糖（LPS）全身性炎症和鱼藤酮（ROT）神经毒性在加重DA神经元损伤中的协同作用。雄性SD成年大鼠接受单次腹腔内注射LPS。7个月后，大鼠皮下注射ROT，每周5次，连续4周。通过转棒和旷场试验评估大鼠行为变化。脑SN进行免疫染色，以评估DA神经元的损失和小胶质细胞的活化。采用高效液相色谱-电化学法测定纹状体DA及其代谢产物的含量。Western blotting法检测α-突触核蛋白（α-Syn）、炎症因子及丝裂原活化蛋白激酶（MAPK）通路的蛋白水平。结果表明，对照组和单独LPS组之间没有显着差异。与单纯ROT组相比，LPS联合ROT组大鼠运动活动明显减少，黑质DA能神经元丢失，纹状体DA及其代谢产物含量降低。LPS联合ROT可促进小胶质细胞活化，增加α-Syn和炎症因子的表达，并激活MAPK信号通路。然而，单独的LPS对上述参数没有显著影响。这些发现表明，成年期暴露于LPS加剧了SN中ROT的神经毒性和炎症作用。
Parkinson’s disease (PD) is the second most neurodegenerative disorder with a regional decrease of dopamine (DA) neurons in the substantia nigra (SN). Despite intense exploration, the etiology of PD progressive process remains unclear. This study was to investigate the synergistic effects of systemic inflammation of lipopolysaccharide (LPS) and neurotoxicity of rotenone (ROT) on exacerbating DA neuron lesion. Male SD adulthood rats received a single intraperitoneal injection of LPS. Seven months later, rats were subcutaneously given ROT five times a week for consecutive 4 weeks. Rat behavior changes were assessed via rotarod and open-field tests. Brain SN was immunostained to evaluate DA neuronal loss and microglia activation. Striatum DA and its metabolites levels were determined by high performance liquid chromatography (HPLC) coupled with electrochemistry. The protein levels of α-synuclein (α-Syn), inflammatory factors and mitogen-activated protein kinase (MAPK) pathway activation were detected by western blotting analysis. Results indicated that no significant difference between the control and LPS alone groups was shown. Compared with ROT alone group, LPS combined with ROT significantly reduced motor activity and induced SN DA neurons loss accompanied by the decreased contents of striatum DA and its metabolites. Furthermore, LPS together with ROT enhanced microglia activation and the increased expressions of α-Syn and inflammatory factors and also MAPK signaling pathway activation. However, LPS alone had no significant effects on the above parameters. These findings suggest that adulthood exposure to LPS exacerbates the neurotoxic and inflammatory effects of ROT in the SN.