Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease

Paraskevi Krashia, Alberto Cordella, Annalisa Nobili, Livia La Barbera, Mauro Federici, Alessandro Leuti, Federica Campanelli, Giuseppina Natale, Gioia Marino, Valeria Calabrese, Francescangelo Vedele, Veronica Ghiglieri, Barbara Picconi, Giulia Di Lazzaro, Tommaso Schirinzi, Giulia Sancesario, Nicolas Casadei, Olaf Riess, Sergio Bernardini, Antonio Pisani, Paolo Calabresi, Maria Teresa Viscomi, Charles Nicholas Serhan, Valerio Chiurchiù, Marcello D’Amelio and Nicola Biagio Mercuri ()
Additional contact information
Paraskevi Krashia: IRCCS Santa Lucia Foundation
Alberto Cordella: IRCCS Santa Lucia Foundation
Annalisa Nobili: IRCCS Santa Lucia Foundation
Livia La Barbera: IRCCS Santa Lucia Foundation
Mauro Federici: IRCCS Santa Lucia Foundation
Alessandro Leuti: IRCCS Santa Lucia Foundation
Federica Campanelli: IRCCS Santa Lucia Foundation
Giuseppina Natale: IRCCS Santa Lucia Foundation
Gioia Marino: IRCCS Santa Lucia Foundation
Valeria Calabrese: IRCCS Santa Lucia Foundation
Francescangelo Vedele: IRCCS Santa Lucia Foundation
Veronica Ghiglieri: IRCCS Santa Lucia Foundation
Barbara Picconi: IRCCS Santa Lucia Foundation
Giulia Di Lazzaro: University of Rome ‘Tor Vergata’
Tommaso Schirinzi: University of Rome ‘Tor Vergata’
Giulia Sancesario: IRCCS Santa Lucia Foundation
Nicolas Casadei: Institute of Medical Genetics and Applied Genomics, University of Tübingen
Olaf Riess: Institute of Medical Genetics and Applied Genomics, University of Tübingen
Sergio Bernardini: University of Rome ‘Tor Vergata’
Antonio Pisani: IRCCS Santa Lucia Foundation
Paolo Calabresi: IRCCS Santa Lucia Foundation
Maria Teresa Viscomi: Institute of Histology and Embryology, Università Cattolica del Sacro Cuore
Charles Nicholas Serhan: Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School
Valerio Chiurchiù: IRCCS Santa Lucia Foundation
Marcello D’Amelio: IRCCS Santa Lucia Foundation
Nicola Biagio Mercuri: IRCCS Santa Lucia Foundation

Nature Communications, 2019, vol. 10, issue 1, 1-19

Abstract: Abstract Neuroinflammation is one of the hallmarks of Parkinson’s disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD – to modulate disease progression – still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.

Date: 2019
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DOI: 10.1038/s41467-019-11928-w

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