Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra
Open accessAbstract
The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1beta (IL-1beta) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1beta in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1beta in the adult rat SN using a recombinant adenovirus expressing IL-1beta. The chronic expression of IL-1beta for 60 days induced dopaminergic cell death in the SN and unilateral akinesia starting only at 21 days post-injection. Microglial cell activation and inflammatory cell infiltrate were associated with dopaminergic cell death and motor disabilities. Astrocytic activation was delayed and associated with scar formation. The chronic expression of a single proinflammatory cytokine as IL-1beta in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1beta per se is able to mediate inflammatory-mediated toxic effects in the SN if its expression is sustained. This model will be helpful to identify possible therapeutic targets related to inflammation-derived neurodegeneration in the SN.
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Chronic expression of IL-1β in substantia nigra of rats induced progressive death of dopaminergic neurons and motor impairments.
“Moreover, the chronic expression of IL-1β in substantia nigra of rats induced progressive death of dopaminergic neurons and resulted in motor impairments (241).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [241]
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- Authors
- Ferrari, C. C., Pott Godoy, M. C., Tarelli, R., Chertoff, M., Depino, A. M., & Pitossi, F. J.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Pitossi, Fernando Juan
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 24
- Issue
- 1
- Pages
- 183-193
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2046088592
- Cited by
- 235
- References
- 59
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 18 · 2022: 20 · 2021: 16 · 2020: 20 · 2019: 9 · 2018: 13 · 2017: 11 · 2016: 9 · 2015: 14 · 2014: 10 · 2013: 11 · 2012: 9
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Consejo Nacional de Investigaciones Científicas y Técnicas
- 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
- IL-1β, substantia nigra, Parkinson's disease, neuroinflammation, dopaminergic neuron loss, akinesia, microglial activation, astrocyte activation, glial scar formation, adenoviral gene expression, motor impairment, neurodegeneration
- MeSH terms
- Adenoviridae, Animals, Astrocytes, Dopamine, Genetic Vectors, Glial Fibrillary Acidic Protein, Interleukin-1, Macrophage Activation, Macrophages, Male, Motor Activity, Movement Disorders, Nerve Degeneration, Neuroglia, Neurons, Parkinson Disease, Secondary, Substantia Nigra, Cytokines, Cell Death, Rats, Wistar, Microglia, Rats
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