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

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....

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Vydáno v:	Nature communications Ročník 10; číslo 1; s. 3945 - 19
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 02.09.2019 Nature Publishing Group Nature Portfolio
Témata:	13/1 13/21 13/31 13/51 14 14/19 14/63 631/250/371 631/378/1689/1718 64 64/86 9/30 9/74 alpha-Synuclein - genetics alpha-Synuclein - metabolism Animals Degeneration Disease Models, Animal Docosahexaenoic Acids - administration & dosage Docosahexaenoic Acids - genetics Docosahexaenoic Acids - metabolism Dopamine Dopamine D1 receptors Dopaminergic Neurons - drug effects Dopaminergic Neurons - metabolism Humanities and Social Sciences Humans Inflammation Inflammation - prevention & control Male Mesencephalon Microglia Microglia - drug effects Microglia - metabolism Movement disorders multidisciplinary Neostriatum Nerve Degeneration - prevention & control Neurodegeneration Neurodegenerative diseases Outflow Parkinson Disease - genetics Parkinson Disease - metabolism Parkinson Disease - prevention & control Parkinson's disease Rats Rats, Sprague-Dawley Rats, Transgenic Science Science (multidisciplinary) Substantia nigra Substantia Nigra - drug effects Substantia Nigra - metabolism Synuclein γ-Interferon
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. Resolvins are endogenous lipids with pro-resolving activity. Here the authors find that rats overexpressing human α-synuclein show defects in dopamine signalling before dopamine cell loss, and that this is associated with low Resolvin D1 levels and neuroinflammation.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-11928-w