TY - JOUR
T1 - Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson's disease.
AU - Krashia, Paraskevi
AU - Cordella, Alberto
AU - Nobili, Annalisa
AU - La Barbera, Livia
AU - Federici, Mauro
AU - Leuti, Alessandro
AU - Campanelli, Federica
AU - Natale, Giuseppina
AU - Marino, Gioia
AU - Calabrese, Valeria
AU - Vedele, Francescangelo
AU - Ghiglieri, Veronica
AU - Picconi, Barbara
AU - Di Lazzaro, Giulia
AU - Schirinzi, Tommaso
AU - Sancesario, Giulia
AU - Casadei, Nicolas
AU - Riess, Olaf
AU - Bernardini, Sergio
AU - Pisani, Antonio
AU - Calabresi, Paolo
AU - Viscomi, Maria Teresa
AU - Serhan, Charles Nicholas
AU - Chiurchiù, Valerio
AU - D’Amelio, Marcello
AU - Mercuri, Nicola Biagio
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - neuroinflammation
KW - neuroinflammation
UR - http://hdl.handle.net/10807/147368
U2 - 10.1038/s41467-019-11928-w
DO - 10.1038/s41467-019-11928-w
M3 - Article
SN - 2041-1723
VL - 10
SP - 4725
EP - 4725
JO - Nature Communications
JF - Nature Communications
ER -
