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Cited by 53Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersNF-κB Signaling Pathways

Microglia activation contributes to quinolinic acid-induced neuronal excitotoxicity through TNF-α

Feng, Wei, Wang, Yan, Liu, Zi-Qi, Zhang, Xuan, Han, Rong, Miao, You-Zhu, Qin, Zheng-Hong·2017·Apoptosis
DOI 10.1007/s10495-017-1363-5
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Abstract

It has been reported that activation of NF-κB is involved in excitotoxicity; however, it is not fully understood how NF-κB contributes to excitotoxicity. The aim of this study is to investigate if NF-κB contributes to quinolinic acid (QA)-mediated excitotoxicity through activation of microglia. In the cultured primary cortical neurons and microglia BV-2 cells, the effects of QA on cell survival, NF-κB expression and cytokines production were investigated. The effects of BV-2-conditioned medium (BCM) on primary cortical neurons were examined. The effects of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, and minocycline (MC), an inhibitor of microglia activation, on QA-induced excitotoxicity were assessed. QA-induced NF-κB activation and TNF-α secretion, and the roles of TNF-α in excitotoxicity were studied. QA at the concentration below 1 mM had no apparent toxic effects on cultured primary neurons or BV-2 cells. However, addition of QA-primed BCM to primary neurons did aggravate QA-induced excitotoxicity. The exacerbation of QA-induced excitotoxicity by BCM was partially ameliorated by inhibiting NF-κB and microglia activation. QA induced activation of NF-κB and upregulation of TNF-α in BV-2 cells. Addition of recombinant TNF-α mimicked QA-induced excitotoxic effects on neurons, and neutralizing TNF-α with specific antibodies partially abolished exacerbation of QA-induced excitotoxicity by BCM. These studies suggested that QA activated microglia and upregulated TNF-α through NF-κB pathway in microglia. The microglia-mediated inflammatory pathway contributed, at least in part, to QA-induced excitotoxicity.

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  • Metabolism of tryptophan by activated microglia produces the neurotoxin quinolinic acid, an N-methyl-D-aspartate agonist implicated in several neurological conditions including Huntington's disease and depression.

    “Metabolism of tryptophan by activated microglia produces the neurotoxin quinolinic acid, an N-methyl-D-aspartate agonist implicated in several neurological conditions including Huntington’s disease and depression (Feng et al., 2017).”

    From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as Feng et al., 2017

  • Tryptophan is a serotonin precursor.

    “Another microbial metabolite that influences microglia activity is tryptophan, a serotonin precursor.”

    From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as Feng et al., 2017

  • Metabolism of tryptophan by activated microglia produces the neurotoxin quinolinic acid, an N-methyl-d-aspartate agonist, implicated in several neurological conditions, including Huntington's disease and depression.

    “More recently, it has also been reported that metabolism of tryptophan by activated microglia produces the neurotoxin quinolinic acid, an N-methyl-d-aspartate agonist, implicated in several neurological conditions, including Huntington’s disease and depression (90).”

    From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [90]

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Authors
Feng, W., Wang, Y., Liu, Z.-Q., Zhang, X., Han, R., Miao, Y.-Z., & Qin, Z.-H.
Affiliations
  • Soochow University (CN)
  • Harvard University (US)
Corresponding author
Qin, Zheng-Hong
ORCID
Venue
Apoptosis
Publisher
Springer Science and Business Media LLC
Published
2017-03-17
Volume
22
Issue
5
Pages
696-709
ISSN
  • 1360-8185 (ISSN-L)
  • 1573-675X
DOI
10.1007/s10495-017-1363-5
OpenAlex
W2596435933
Cited by
53
References
72
Citations by year
2026: 8 · 2025: 8 · 2024: 6 · 2023: 2 · 2022: 9 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 2
FWCI
1.91
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • APOPTOSIS (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81671252, 30930035)
  • National Natural Science Foundation of China (CN) (81000547)
  • National key basic science project 973 project (2011CB510003)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
quinolinic acid, excitotoxicity, microglial activation, NF-κB signaling, TNF-α, neuroinflammation, conditioned medium, pyrrolidine dithiocarbamate, minocycline, cortical neurons, BV-2 cells
MeSH terms
Animals, Cell Survival, Gene Expression Regulation, Inflammation, Minocycline, Neurons, Neurotoxins, Pyrrolidines, Quinolinic Acids, Thiocarbamates, Tumor Necrosis Factor-alpha, NF-kappa B, Apoptosis, Microglia, Rats, Primary Cell Culture

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