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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

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

Sadayuki Hashioka1, Andis Klegeris, Akira Monji

  • 1Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan. hashioka@interchange.ubc.ca

Experimental Neurology
|May 8, 2007
PubMed

Insights

Antidepressants inhibit pro-inflammatory mediators from activated microglia, suggesting a therapeutic role in depression. Lithium chloride, however, shows mixed effects on microglial activation pathways.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Activated microglia and pro-inflammatory cytokines are implicated in depression pathogenesis.
  • Interferon-gamma (IFN-gamma) activates microglia, increasing pro-inflammatory mediator production.

Purpose of the Study:

  • To investigate the effects of antidepressants and lithium chloride on IFN-gamma-induced microglial activation.
  • To elucidate the involvement of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) pathways.

Main Methods:

  • Murine microglial 6-3 cells were treated with IFN-gamma to induce IL-6 and NO production.
  • Cells were pretreated with various antidepressants (fluvoxamine, reboxetine, imipramine) and lithium chloride.
  • Inhibitory effects were assessed, and involvement of cAMP/PKA pathways was tested using specific inhibitors (SQ 22536, Rp-3',5'-cAMPS).

Main Results:

  • IFN-gamma significantly increased IL-6 and NO production.
  • Antidepressants dose-dependently inhibited IL-6 and NO production, effects partially mediated by cAMP/PKA.
  • Lithium chloride enhanced IL-6 but inhibited NO production, independent of cAMP/PKA pathways.

Conclusions:

  • Antidepressants exhibit inhibitory effects on activated microglia, potentially via the cAMP-dependent PKA pathway, offering a novel therapeutic insight for depression.
  • Lithium chloride demonstrates differential effects on microglial activation, highlighting its complex mechanism of action as a mood stabilizer.

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