The current study sought to characterize the pro-survival effects of erythropoietin (EPO) in a toxicant model of Parkinson's disease (PD). EPO treatment induced time-dependent elevations of antioxidant glutathione peroxidase (GPx) and anti-apoptotic factors (pAkt and pBad/Bad) within the striatum and substantia nigra pars compacta (SNc). Intriguingly, our results indicated a region- and lesion size- dependence of pro-survival effects of EPO. Indeed, intra-striatal (but not intra-nigral) infusion of EPO was effective at preventing dopaminergic terminal degeneration and sSNc neuronal loss induced by two different doses of 6-OHDA. These neuroprotective consequences were paralleled by a diminution of microglial morphological changes, along with enhanced motor functioning seen through a reduction in apomorphine-induced rotational behaviour. Finally, in the context of the 6-OHDA lesion, EPO again induced anti-apoptotic (Bcl-2) and antioxidant (GPx) factors within the striatum. Taken together, these results raise the possibility of EPO's potential use as an adjuvant therapy in the treatment of PD, or at least, suggest possible brain-region specific targets for the protective effects of EPO.

目前的研究试图表征促红细胞生成素 (EPO) 在帕金森病 (PD) 毒物模型中的促生存作用。EPO 处理诱导纹状体和黑质致密部 (SNc) 内抗氧化谷胱甘肽过氧化物酶 (GPx) 和抗凋亡因子 (pAkt 和 pBad/Bad) 的时间依赖性升高。有趣的是，我们的结果表明 EPO 的促生存作用存在区域和病变大小依赖性。事实上，纹状体内（但不是黑质内）输注 EPO 可有效预防由两种不同剂量的 6-OHDA 诱导的多巴胺能终末变性和 sSNc 神经元丢失。这些神经保护作用伴随着小胶质细胞形态变化的减少，以及通过阿扑吗啡诱导的旋转行为的减少所看到的运动功能的增强。最后，在 6-OHDA 病变的背景下，EPO 再次诱导纹状体内的抗凋亡 (Bcl-2) 和抗氧化 (GPx) 因子。总之，这些结果提高了 EPO 作为 PD 治疗辅助疗法的潜在用途的可能性，或者至少表明了 EPO 保护作用的可能的脑区域特异性靶标。