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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Published in:Nature communications Vol. 10; no. 1; pp. 3945 - 19
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 02.09.2019
Nature Publishing Group
Nature Portfolio
Subjects:
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13/21
13/31
13/51
14
14/19
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631/250/371
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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
Online Access:Get full text
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Summary: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-11928-w