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 PisaniPaolo Calabresi, Maria Teresa Viscomi, Charles Nicholas Serhan, Valerio Chiurchiù, Marcello D’Amelio, Nicola Biagio Mercuri

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number3945
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Parkinson disease
pathology
Pathology
dopamine
rats
Parkinson Disease
Rats
Synucleins
Inflammation
degeneration
Dopaminergic Neurons
Dopamine
neurons
Neurons
Corpus Striatum
Nerve Degeneration
Microglia
Substantia Nigra
Mesencephalon
progressions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease. / Krashia, Paraskevi; Cordella, Alberto; Nobili, Annalisa; La Barbera, Livia; Federici, Mauro; Leuti, Alessandro; Campanelli, Federica; Natale, Giuseppina; Marino, Gioia; Calabrese, Valeria; Vedele, Francescangelo; Ghiglieri, Veronica; Picconi, Barbara; Di Lazzaro, Giulia; Schirinzi, Tommaso; Sancesario, Giulia; Casadei, Nicolas; Riess, Olaf; Bernardini, Sergio; Pisani, Antonio; Calabresi, Paolo; Viscomi, Maria Teresa; Serhan, Charles Nicholas; Chiurchiù, Valerio; D’Amelio, Marcello; Mercuri, Nicola Biagio.

In: Nature Communications, Vol. 10, No. 1, 3945, 01.12.2019.

Research output: Contribution to journalArticle

Krashia, P, Cordella, A, Nobili, A, La Barbera, L, Federici, M, Leuti, A, Campanelli, F, Natale, G, Marino, G, Calabrese, V, Vedele, F, Ghiglieri, V, Picconi, B, Di Lazzaro, G, Schirinzi, T, Sancesario, G, Casadei, N, Riess, O, Bernardini, S, Pisani, A, Calabresi, P, Viscomi, MT, Serhan, CN, Chiurchiù, V, D’Amelio, M & Mercuri, NB 2019, 'Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease', Nature Communications, vol. 10, no. 1, 3945. https://doi.org/10.1038/s41467-019-11928-w
Krashia, Paraskevi ; Cordella, Alberto ; Nobili, Annalisa ; La Barbera, Livia ; Federici, Mauro ; Leuti, Alessandro ; Campanelli, Federica ; Natale, Giuseppina ; Marino, Gioia ; Calabrese, Valeria ; Vedele, Francescangelo ; Ghiglieri, Veronica ; Picconi, Barbara ; Di Lazzaro, Giulia ; Schirinzi, Tommaso ; Sancesario, Giulia ; Casadei, Nicolas ; Riess, Olaf ; Bernardini, Sergio ; Pisani, Antonio ; Calabresi, Paolo ; Viscomi, Maria Teresa ; Serhan, Charles Nicholas ; Chiurchiù, Valerio ; D’Amelio, Marcello ; Mercuri, Nicola Biagio. / Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson’s disease. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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