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.

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein / 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; Romana Fusco, Francesca; Chiurchiù, Valerio; B Mercuri, Nicola. - In: NPJ PARKINSON'S DISEASE. - ISSN 2373-8057. - (2024).

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein

Sebastian Luca D'Addario;Mauro Federici;Debora Cutuli;Laura Petrosini;Valerio Chiurchiù;
2024

Abstract

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.
2024
Parkinson's disease; aging.
01 Pubblicazione su rivista::01a Articolo in rivista
Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein / 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; Romana Fusco, Francesca; Chiurchiù, Valerio; B Mercuri, Nicola. - In: NPJ PARKINSON'S DISEASE. - ISSN 2373-8057. - (2024).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1731524
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