Cytokine-induced enhancement of calcium-dependent glutamate release from astrocytes mediated by nitric oxide
Abstract
Cytokines are produced in the central nervous system (CNS) and exhibit various effects on neurons, microglia, and astrocytes. Astrocytes can release chemical transmitters, including glutamate, in a calcium-dependent manner, which may mediate communication between neurons and astrocytes. To date, no studies have been conducted on the effects of cytokines on calcium-dependent glutamate release from astrocytes. Here, we studied the effects of cytokines on calcium-dependent glutamate release. Cytokines enhanced glutamate release and induced the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO). The inhibition of iNOS eliminated the cytokine-induced enhancement of glutamate release, and treatment with a NO donor, even in the absence of cytokines, increased glutamate release. Thus, cytokines enhance glutamate release, and this enhancement is mediated by NO.
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Quinolinic acid and inflammatory cytokines increase glutamate release and reduce astrocytic glutamate uptake via the excitatory amino acid transporter.
“QUIN and inflammatory cytokines have also been shown to increase glutamate release and decrease the astrocytic uptake of glutamate by the excitatory amino acid transporter”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Ida et al., 2008
Glutamate release by astrocytes has been shown to be affected by cytokines, potentially leading to excitotoxicity.
“For example, glutamate release by astrocytes has been shown to be affected by cytokines, potentially leading to excitotoxicity (94, 95).”
From Cytokine Research in Depression: Principles, Challenges, and Open Questions (2019) · cites this paper as [94]
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- Authors
- Ida, T., Hara, M., Nakamura, Y., Kozaki, S., Tsunoda, S., & Ihara, H.
- Affiliations
- Osaka Prefecture University (JP)
- Corresponding author
- Ihara, Hideshi
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 432
- Issue
- 3
- Pages
- 232-236
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2018613168
- Cited by
- 107
- References
- 29
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 12 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 5 · 2013: 8 · 2012: 7
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- cytokines, astrocytes, glutamate release, calcium-dependent release, nitric oxide, inducible nitric oxide synthase, neuron-glia communication, nitric oxide donors
- MeSH terms
- Analysis of Variance, Animals, Astrocytes, Calcium, Cells, Cultured, Cerebral Cortex, Embryo, Mammalian, Enzyme Inhibitors, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Nitric Oxide, Triazenes, Cytokines, Rats, Wistar, Glutamic Acid, Rats, Nitric Oxide Synthase Type II
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