Systemic Inflammation Accelerates Neurodegeneration in a Rat Model of Parkinson's Disease Overexpressing Human Alpha Synuclein

Overview

Journal NPJ Parkinsons Dis

Date 2024 Nov 5

PMID 39500895

Authors

Mariangela Massaro Cenere

Marta Tiberi

Emanuela Paldino

Sebastian Luca DAddario

Mauro Federici

Cecilia Giacomet

Debora Cutuli

Alessandro Matteocci

Francesca Cossa

Beatrice Zarrilli

Nicolas Casadei

Ada Ledonne

Laura Petrosini

Nicola Berretta

Francesca Romana Fusco

Valerio Chiurchiu

Nicola B Mercuri

Affiliations

Soon will be listed here.

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.

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