Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson’s disease (PD). In the present study, we assessed the development of symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca^+/+) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT and Snca^+/+ rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes. However, only LPS Snca^+/+ rats showed dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), associated with a reduction in the release of evoked dopamine in the striatum. No significant changes were observed in the behavioral domain. We propose our double-hit animal as a reliable model to investigate the mechanisms whereby α-synuclein and inflammation interact to promote neurodegeneration in PD.

人们越来越努力阐明遗传和环境因素在帕金森病 （PD） 中如何相互作用。在本研究中，我们评估了在症状前过表达人 α-突触核蛋白 （Snca^+/+） 的遗传 PD 大鼠模型上的症状发展，通过腹膜内注射脂多糖 （LPS） 暴露于促炎损伤，使用免疫组织学、高维流式细胞术、恒电位安培法和行为分析。向 WT 和 Snca^+/+ 大鼠单次注射 LPS 触发了促炎小胶质细胞标志物、单核细胞和 T 淋巴细胞活化的长期增加。然而，只有 LPS Snca ^{+ / +} 大鼠在黑质致密部 （SNpc） 中显示多巴胺能神经元丢失，与纹状体中诱发多巴胺释放的减少有关。在行为领域没有观察到显着变化。我们建议将我们的双重打击动物作为一个可靠的模型来研究 α-突触核蛋白和炎症相互作用以促进 PD 神经退行性变的机制。