Neuroinflammation mediated by IL-1β increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease
Open accessAbstract
Background: The etiology of Parkinson's disease (PD) remains elusive despite identification of several genetic mutations. It is more likely that multiple factors converge to give rise to PD than any single cause. Here we report that inflammation can trigger degeneration of dopamine (DA) neurons in an animal model of Parkinson's disease. Methods: We examined the effects of inflammation on the progressive 6-OHDA rat model of Parkinson's disease using immunohistochemistry, multiplex ELISA, and cell counting stereology. Results: We show that a non-toxic dose of lipopolysaccharide (LPS) induced secretion of cytokines and predisposed DA neurons to be more vulnerable to a subsequent low dose of 6-hydroxydopamine. Alterations in cytokines, prominently an increase in interleukin-1beta (IL-1β), were identified as being potential mediators of this effect that was associated with activation of microglia. Administration of an interleukin-1 receptor antagonist resulted in significant reductions in tumor necrosis factor-α and interferon-γ and attenuated the augmented loss of DA neurons caused by the LPS-induced sensitization to dopaminergic degeneration. Conclusion: These data provide insight into the etiology of PD and support a role for inflammation as a risk factor for the development of neurodegenerative disease.
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In a different PD mouse model, blocking IL-1β signaling using an IL-1 receptor antagonist significantly attenuated neurodegeneration.
“In a different PD mouse model, blocking IL-1β signaling using an IL-1 receptor antagonist also significantly attenuated neurodegeneration.362,363”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [362]
The Results section reports significantly less dopamine-neuron cell loss with IL-1 receptor antagonist than with vehicle after LPS and 6-OHDA treatment (p < 0.05). However, the Background identifies the model as a rat model of Parkinson’s disease, not a mouse model. (LLM, conf=0.91)
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- Authors
- Koprich, J. B., Reske-Nielsen, C., Mithal, P., & Isacson, O.
- Affiliations
- Harvard University (US)
- ORCID
- Koprich, James B
- Venue
- Journal of Neuroinflammation
- Published
- 2008-02-27
- Volume
- 5
- Issue
- 1
- Pages
- 8-8
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC2292163
- OpenAlex
- W1990872391
- Cited by
- 355
- References
- 86
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 27 · 2023: 18 · 2022: 30 · 2021: 24 · 2020: 22 · 2019: 15 · 2018: 21 · 2017: 15 · 2016: 21 · 2015: 22 · 2014: 16 · 2013: 19 · 2012: 14
- FWCI
- 13.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P50NS039793, NS-39793)
- 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, IL-1β, dopaminergic neurons, dopaminergic neuron loss, lipopolysaccharide, 6-hydroxydopamine, microglial activation, interleukin-1 receptor antagonist, TNF-α, interferon-gamma, neurodegeneration, Parkinson's disease model
- MeSH terms
- Animals, Disease Models, Animal, Disease Susceptibility, Dopamine, Female, Lipopolysaccharides, Nerve Degeneration, Neuritis, Risk Factors, Substantia Nigra, Sympatholytics, Neuroimmunomodulation, Oxidopamine, Rats, Sprague-Dawley, Microglia, Antirheumatic Agents, Parkinsonian Disorders, Rats, Interleukin-1beta, Interleukin 1 Receptor Antagonist Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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