Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson's disease.
Animals
Disease Models, Animal
Docosahexaenoic Acids
/ administration & dosage
Dopaminergic Neurons
/ drug effects
Humans
Inflammation
/ prevention & control
Male
Microglia
/ drug effects
Nerve Degeneration
/ prevention & control
Parkinson Disease
/ genetics
Rats
Rats, Sprague-Dawley
Rats, Transgenic
Substantia Nigra
/ drug effects
alpha-Synuclein
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 09 2019
02 09 2019
Historique:
received:
03
09
2018
accepted:
12
08
2019
entrez:
4
9
2019
pubmed:
4
9
2019
medline:
31
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31477726
doi: 10.1038/s41467-019-11928-w
pii: 10.1038/s41467-019-11928-w
pmc: PMC6718379
doi:
Substances chimiques
SNCA protein, human
0
alpha-Synuclein
0
resolvin D1
0
Docosahexaenoic Acids
25167-62-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3945Subventions
Organisme : NIGMS NIH HHS
ID : P01 GM095467
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM038765
Pays : United States
Commentaires et corrections
Type : ErratumIn
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