Parkinson’s disease is a neurodegenerative disorder characterized by the progressive death of dopaminergic (DA) neurons in the substantia nigra (SN), which leads to a loss of the neurotransmitter dopamine in the basal ganglia. Current treatments relieve the symptoms of the disease, but none stop or delay neuronal degeneration. Liver growth factor (LGF) is an albumin–bilirubin complex that stimulates axonal growth in the striatum and protects DA neurons in the SN of 6-hydroxydopamine-lesioned rats. Our previous results suggested that these effects observed in vivo are mediated by microglia and/or astrocytes. To determine if these cells are LGF targets, E14 (embryos from Sprague Dawley rats of 14 days) rat mesencephalic glial cultures were used. Treatment with 100 pg/mL of LGF up-regulated the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases 1/2 (ERK1/2) and the cyclic AMP response element binding protein (CREB) phosphorylation in glial cultures, and it increased the microglia marker Iba1 and tumor necrosis factor alpha (TNF-alpha) protein levels. The treatment of E14 midbrain neurons with a glial-conditioned medium from LGF-treated glial cultures (GCM-LGF) prevented the loss of DA neurons caused by 6-hydroxy-dopamine. This neuroprotective effect was not observed when GCM-LGF was applied in the presence of a blocking antibody of TNF-alpha activity. Altogether, our findings strongly suggest the involvement of microglia and TNF-alpha in the neuroprotective action of LGF on DA neurons observed in vitro.

中文翻译：

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在帕金森氏病的体外模型中，肝生长因子诱导神经胶质相关的神经保护作用。

帕金森氏病是一种神经退行性疾病，其特征是黑质（SN）中的多巴胺能（DA）神经元进行性死亡，从而导致基底神经节中神经递质多巴胺的丧失。当前的疗法减轻了疾病的症状，但是没有一种疗法能够阻止或延迟神经元变性。肝生长因子（LGF）是一种白蛋白-胆红素复合物，可刺激纹状体中轴突生长并保护6-羟基多巴胺损伤大鼠的SN中的DA神经元。我们以前的结果表明，体内观察到的这些作用是由小胶质细胞和/或星形胶质细胞介导的。为了确定这些细胞是否为LGF靶标，使用了E14（来自Sprague Dawley大鼠的14天胚胎）大鼠中脑神经胶质培养物。用100 pg / mL的LGF处理可在胶质细胞培养物中上调丝裂原激活的蛋白激酶（MAPK），细胞外信号调节的激酶1/2（ERK1 / 2）和环状AMP响应元件结合蛋白（CREB）的磷酸化，以及它增加了小胶质细胞标志物Iba1和肿瘤坏死因子α（TNF-alpha）的蛋白质水平。用来自LGF处理的神经胶质培养物（GCM-LGF）的神经胶质条件培养基处理E14中脑神经元，可以防止由6-羟基多巴胺引起的DA神经元的丢失。当在TNF-α活性的封闭抗体存在下应用GCM-LGF时，未观察到这种神经保护作用。总之，我们的发现强烈暗示小胶质细胞和TNF-α参与了LGF对体外观察到的DA神经元的神经保护作用。