Modulation of microglial activation by antidepressants
Nicole Mariani1, James Everson1, Carmine M Pariante1
1Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Journal of Psychopharmacology (Oxford, England)
|January 31, 2022
Summary
Antidepressants can regulate microglial activation, a key factor in depression pathogenesis. This review found that most antidepressant classes reduce neuroinflammation and oxidative stress, suggesting a novel therapeutic mechanism.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Microglial activation and neuroinflammation are implicated in depression.
- This involves changes in microglial morphology, cytokine release, and oxidative stress.
- Antidepressants may target these neuroinflammatory pathways.
Purpose of the Study:
- To review in vitro and ex vivo studies on antidepressant effects on microglial activation.
- To examine cellular changes and signaling molecules in microglia models of neuroinflammation.
- To synthesize findings from studies using lipopolysaccharide (LPS) or cytokine stimulation.
Main Methods:
- Systematic review of 23 in vitro and ex vivo studies.
- Analysis of studies using LPS or cytokine-induced neuroinflammation models.
- Assessment of microglial activation markers, including cellular changes and molecular signaling.
Main Results:
- Most antidepressants (SSRIs, SNRIs, MAOIs, TCAs) inhibited microglial activation.
- Reduced microglial reactivity, immune, and oxidative stress products were observed.
- Some antidepressants (bupropion, agomelatine) were ineffective against IFN-γ-induced activation; others showed inconsistent results.
Conclusions:
- Antidepressant action may involve the regulation of microglial activation.
- This mechanism is particularly relevant in the context of heightened inflammation.
- Findings support a role for targeting neuroinflammation in depression treatment.
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