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Cited by 198Tryptophan and brain disordersNeuroinflammation and Neurodegeneration MechanismsTreatment of Major Depression

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Antidepressants inhibit interferon-γ-induced microglial production of IL-6 and nitric oxide

Hashioka, Sadayuki, Klegeris, Andis, Monji, Akira, Kato, Takahiro, Sawada, Makoto, McGeer, Patrick L., Kanba, Shigenobu·2007·Experimental Neurology
DOI 10.1016/j.expneurol.2007.03.022
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Abstract

Circumstantial evidence has suggested that activated microglia may be associated with the pathogenesis of depression. Pro-inflammatory cytokines may also be involved. Therefore, we examined the effects of various types of antidepressants, as well as the mood-stabilizer lithium chloride, on interferon-gamma (IFN-gamma)-induced microglial production of the pro-inflammatory mediators interleukin-6 (IL-6) and nitric oxide (NO). Treatment of the murine microglial 6-3 cells with 100 U/ml of IFN-gamma resulted in an eightfold increase in IL-6 and a tenfold increase in NO into the culture medium. Pretreatment with the selective serotonin reuptake inhibitor fluvoxamine, the relatively selective noradrenaline reuptake inhibitor reboxetine, or the non-selective monoaminergic reuptake inhibitor imipramine, significantly inhibited IL-6 and NO production in a dose-dependent manner. These inhibitions were reversed significantly by SQ 22536, a cyclic adenosine monophosphate (cAMP) inhibitor, and, except for reboxetine, by the protein kinase A (PKA) inhibitor Rp-adenosine3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-3',5'-cAMPS). Lithium chloride, which is believed to act by inhibiting the calcium-dependent release of noradrenaline, had a different spectrum of action on microglial 6-3 cells. It enhanced IFN-gamma-stimulated IL-6 production and inhibited NO production. The inhibitory effect of lithium chloride was not reversed by either SQ 22536 or Rp-3',5'-cAMPS. These results suggest that antidepressants have inhibitory effects on IFN-gamma-activated microglia and these effects are, at least partially, mediated by the cAMP-dependent PKA pathway. On the other hand, the mood stabilizer and anti-manic agent lithium chloride has mixed effects on IFN-gamma-induced microglial activation.

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Crossref · 10.1016/j.expneurol.2007.03.022

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Metadata

Authors
Hashioka, S., Klegeris, A., Monji, A., Kato, T., Sawada, M., McGeer, P. L., & Kanba, S.
Affiliations
  • Kyushu University (JP)
  • University of British Columbia (CA)
  • Research Institute of Environmental Medicine, Nagoya University (JP)
Corresponding author
  • Hashioka, Sadayuki
  • Monji, Akira
ORCID
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2007-07
Volume
206
Issue
1
Pages
33-42
ISSN
0014-4886 (ISSN-L)
DOI
10.1016/j.expneurol.2007.03.022
OpenAlex
W1970022478
Cited by
198
References
42
Citations by year
2026: 3 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 10 · 2018: 5 · 2017: 7 · 2016: 18 · 2015: 16 · 2014: 18 · 2013: 14 · 2012: 18
FWCI
3.53
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
antidepressants, microglia, interferon-gamma, interleukin-6, nitric oxide, fluvoxamine, reboxetine, imipramine, lithium chloride, cAMP signaling, protein kinase A, microglial activation, depression, inflammatory cytokines, mood stabilizers
MeSH terms
Cyclic AMP, Animals, Antidepressive Agents, Antiviral Agents, Brain, Cell Line, Depressive Disorder, Dose-Response Relationship, Drug, Enzyme Inhibitors, Interferon-gamma, Mice, Inbred C57BL, Nitric Oxide, Neurotransmitter Uptake Inhibitors, Interleukin-6, Up-Regulation, Microglia, Cyclic AMP-Dependent Protein Kinases, Lithium Chloride, Antimanic Agents, MAP Kinase Signaling System, Mice, Cyclic AMP-Dependent Protein Kinase Type II

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