Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration.
Abstract
The loss of dopaminergic neurones in the substantia nigra with Parkinson's disease may result from inflammation-induced proliferation of microglia and reactive macrophages expressing inducible nitric oxide synthase (iNOS). We have investigated the effects of the supranigral administration of lipopolysaccharide on iNOS-immunoreactivity, 3-nitrotyrosine formation and tyrosine hydroxylase-immunoreactive neuronal number, and retrogradely labelled fluorogold-positive neurones in the ventral mesencephalon in male Wistar rats. Following supranigral lipopolysaccharide injection, 16-18 h previously, there was intense expression of NADPH-diaphorase and iNOS-immunoreactivity in non-neuronal, macrophage-like cells. This was accompanied by intense expression of glial fibrillary acidic protein-immunoreactive astrocytosis in the substantia nigra. There were also significant reductions in the number of tyrosine hydroxylase(50-60%)- and fluorogold (65-75%)-positive neurones in the substantia nigra. In contrast, tyrosine hydroxylase-immunoreactivity in the ventral tegmental area was not altered. Pre-treatment of animals with the iNOS inhibitor, S-methylisothiourea (10 mg kg(-1), i.p.), led to a significant reduction of lipopolysaccharide-induced cell death. Similar reduction of tyrosine hydroxylase-immunoreactivity and fluorogold-labelled neurones in the substantia nigra following lipopolysaccharide administration suggests dopaminergic cell death rather than down-regulation of tyrosine hydroxy…
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These same compounds have also been implicated in the neural tissue damage induced by injection of LPS in rodent brain.
“These same compounds have also been implicated in the neural tissue damage induced by injection of LPS in rodent brain (Iravani et al., 2002;Cai et al., 2003;Arai et al., 2004;Qin et al., 2004).”
From Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase (2008) · cites this paper as Iravani et al., 2002
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Self-citation
- Authors
- Iravani, M. M., Kashefi, K., Mander, P., Rose, S., & Jenner, P.
- Affiliations
- King's College London (GB)
- Corresponding author
- Jenner, P
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 110
- Issue
- 1
- Pages
- 49-58
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2038814798
- Cited by
- 247
- References
- 3
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 8 · 2018: 7 · 2017: 4 · 2016: 5 · 2015: 10 · 2014: 8 · 2013: 11 · 2012: 9
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- inducible nitric oxide synthase, dopaminergic neuron loss, Parkinson's disease, substantia nigra, lipopolysaccharide, neuroinflammation, microglia, macrophages, nitrotyrosine, nitrosative stress, tyrosine hydroxylase, S-methylisothiourea, astrocyte activation, ventral tegmental area
- MeSH terms
- Animals, Cell Count, Dopamine, Encephalitis, Fluorescent Dyes, Glial Fibrillary Acidic Protein, Lipopolysaccharides, Macrophages, Male, NADPH Dehydrogenase, Neurons, Nitric Oxide, Parkinson Disease, Substantia Nigra, Tyrosine 3-Monooxygenase, Cell Death, Rats, Wistar, Hydroxyl Radical, Oxidative Stress, Nitric Oxide Synthase, Peroxynitrous Acid, Rats
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