Massaro Cenere Mariangela, Tiberi Marta, Paldino Emanuela, D'Addario Sebastian Luca, Federici Mauro, Giacomet Cecilia, Cutuli Debora, Matteocci Alessandro, Cossa Francesca, Zarrilli Beatrice, Casadei Nicolas, Ledonne Ada, Petrosini Laura, Berretta Nicola, Fusco Francesca Romana, Chiurchiù Valerio, Mercuri Nicola B
Department of Experimental Neuroscience, Santa Lucia Foundation IRCCS, Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
NPJ Parkinsons Dis. 2024 Nov 5;10(1):213. doi: 10.1038/s41531-024-00824-w.
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.
人们已做出越来越多的努力来阐明遗传和环境因素在帕金森病（PD）中是如何相互作用的。在本研究中，我们使用免疫组织学、高维流式细胞术、恒电位安培法和行为分析，评估了一种在症状出现前过度表达人α-突触核蛋白（Snca）的遗传性PD大鼠模型在接受腹腔注射脂多糖（LPS）引起的促炎刺激后的症状发展情况。向野生型（WT）大鼠和Snca大鼠单次注射LPS会引发促炎小胶质细胞标志物、单核细胞和T淋巴细胞的激活持续增加。然而，只有LPS-Snca大鼠在黑质致密部（SNpc）出现多巴胺能神经元丢失，并伴有纹状体中诱发多巴胺释放的减少。在行为方面未观察到显著变化。我们提出我们的双打击动物模型是一种可靠的模型，可用于研究α-突触核蛋白和炎症相互作用促进PD神经退行性变的机制。
