Systemic inflammation triggers long-lasting neuroinflammation and accelerates neurodegeneration in a rat model of Parkinson’s disease overexpressing human α-synuclein

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 PD-like symptoms on a genetic PD rat model overexpressing 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, electrophysiology, and behavioral analyses. A single injection of LPS to both WT and Snca+/+ rats triggered long-lasting increased activation of pro-inflammatory microglial markers, infiltrating monocytes and T-lymphocytes. However, only LPS Snca +/+ rats displayed dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), associated with a reduction of evoked dopamine release 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. ### Competing Interest Statement The authors have declared no competing interest.