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Cited by 122Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsInflammasome and immune disorders

Neurotoxic Effects of Lipopolysaccharide on Nigral Dopaminergic Neurons Are Mediated by Microglial Activation, Interleukin-1β, and Expression of Caspase-11 in Mice

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Arai, Hiroyuki, Furuya, Tsuyoshi, Yasuda, Toru, Miura, Masayuki, Mizuno, Yoshikuni, Mochizuki, Hideki·2004·Journal of Biological Chemistry
DOI 10.1074/jbc.m407328200
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Abstract

The endotoxin lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, selectively induces degeneration of substantia nigral (SN) dopaminergic neurons via activation of microglial cells in rats and mice. Caspase-11 plays a crucial role in LPS-induced septic shock in mice. We examined the mechanism of LPS neurotoxicity on SN dopaminergic neurons in C57BL/6 mice and caspase-11 knockout mice. Mice were stereotaxically injected with LPS into the SN on one side and vehicle into the SN of the other side. Immunohistochemistry, Western blotting analysis, enzyme-linked immunosorbent assay, and reverse transcriptase-PCR were performed to evaluate damage of SN dopaminergic neurons and activation of microglial cells. Intranigral injection of LPS at 1 or 3 microg/microl/site decreased tyrosine hydroxylase-positive neurons and increased microglial cells in the SN compared with the contralateral side injected with vehicle at days 7 and 14 post-injection in C57BL/6 mice. Intranigral injection of LPS at 3 microg/microl/site induced the expression of caspase-11 mRNA in the ventral midbrain at 6, 8, and 12 h post-injection, and the expression of caspase-11-positive cells in the SN at 8 and 12 h post-injection. Moreover, LPS at 3 microg/microl/site increased interleukin-1beta content in the ventral midbrain at 12 and 24 h post-injection. LPS failed to elicit these responses in caspase-11 knockout mice. Our results indicate that the neurotoxic effects of LPS on nigral dopaminergic neurons are mediated by microglial activation, interleukin-1beta, and caspase-11 expression in mice.

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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 Arai et al., 2004

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Authors
Arai, H., Furuya, T., Yasuda, T., Miura, M., Mizuno, Y., & Mochizuki, H.
Affiliations
  • Juntendo University (JP)
  • The University of Tokyo (JP)
Corresponding author
Mochizuki, Hideki
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-12
Volume
279
Issue
49
Pages
51647-51653
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m407328200
OpenAlex
W2127563454
Cited by
122
References
2
Citations by year
2024: 4 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 10
FWCI
6.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
lipopolysaccharide, neurotoxicity, substantia nigra, dopaminergic neurons, microglial activation, IL-1β, caspase-11, neuroinflammation, tyrosine hydroxylase, Parkinson's disease model
MeSH terms
Animals, Brain, Dopamine, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Interleukin-1, Lipopolysaccharides, Mice, Inbred C57BL, Neurons, RNA, Messenger, Substantia Nigra, Time Factors, Tyrosine 3-Monooxygenase, Blotting, Western, Models, Statistical, Microglia, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Caspases, Mice, Rats, Caspases, Initiator

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