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Cited by 188Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

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

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Krashia, Paraskevi, Cordella, Alberto, Nobili, Annalisa, La Barbera, Livia, Federici, Mauro, Leuti, Alessandro, Campanelli, Federica, Natale, Giuseppina +18 more·2019·Nature Communications
DOI 10.1038/s41467-019-11928-wPMC PMC6718379
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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.

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  • Numerous studies in PD animal models have revealed microglia were activated prior to death of dopamine neurons.

    “Indeed, numerous studies in PD animal models have revealed that microglia were activated prior to the death of dopamine neurons.58–60”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [59]

  • RvD1 was found to be decreased in a human α-synuclein overexpression PD rat model and PD patients at early stage; early RvD1 administration inhibited inflammation in the CNS and periphery and attenuated neuronal dysfunction.

    “RvD1 was found to be decreased in human α-synuclein overexpression PD rat model and PD patients at early stage, early RvD1 administration inhibited inflammation in the CNS and peripheral, attenuated neuronal dysfunction.59”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [59]

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Authors
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, M. T., Serhan, C. N., Chiurchiù, V., D’Amelio, M., & Mercuri, N. B.
Affiliations
  • Università Campus Bio-Medico (IT)
  • University of Rome Tor Vergata (IT)
  • Fondazione Santa Lucia (IT)
  • University of Perugia (IT)
  • University of Tübingen (DE)
  • Università Cattolica del Sacro Cuore (IT)
  • Brigham and Women's Hospital (US)
Corresponding author
Mercuri, Nicola Biagio
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-09-02
Volume
10
Issue
1
Pages
3945-3945
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-11928-w
PMC
PMC6718379
OpenAlex
W2970729530
Cited by
188
References
14
Citations by year
2026: 19 · 2025: 19 · 2024: 17 · 2023: 25 · 2022: 33 · 2021: 39 · 2020: 30 · 2019: 5 · 2018: 1
FWCI
18.10
Type
journal article
Language
en
Update notices
correction (2019-10-14)
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by)
Funders
  • Alzheimer's Association (AARG-18-566270)
  • Fondazione Italiana Sclerosi Multipla (GR-2016-02362380, 2017/R/8)
  • Ministero della Salute (RF‐2018‐12365509, GR-2016-02362380, 2018-, RF-2018-12365527, RF-2018, GR-2011-02351457)
  • Collegio Ghislieri di Pavia
  • Nature
  • National Institutes of Health
  • National Institute of General Medical Sciences (P01GM095467, R01GM038765)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, neuroinflammation, resolvin D1, specialized pro-resolving mediators, alpha-synuclein overexpression, dopaminergic neuron loss, microglial activation, interferon-gamma, motor impairment, early-stage Parkinson's disease
MeSH terms
Animals, Disease Models, Animal, Docosahexaenoic Acids, Humans, Inflammation, Male, Nerve Degeneration, Parkinson Disease, Substantia Nigra, Rats, Sprague-Dawley, Microglia, Rats, alpha-Synuclein, Rats, Transgenic, Dopaminergic Neurons

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