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Updated: Jun 15, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Trazodone counteracts the response of microglial cells to inflammatory stimuli
Elisa Chelucci1, Simona Daniele1, Matteo Vergassola2
1Department of Pharmacy, University of Pisa, Pisa, Italy.
Abstract:
Microglia are resident brain cells that regulate neuronal development and innate immunity. Microglia activation participates in the cellular response to neuroinflammation, thus representing a possible target for pharmacological strategies aimed to counteract the onset and progression of brain disorders, including depression. Antidepressant drugs have been reported to reduce neuroinflammation by acting also on glial cells. Herein, the potential anti-inflammatory and neuroprotective effects of trazodone (TRZ) on the microglial human microglial clone 3 (HMC3) cell line were investigated. HMC3 cells were activated by a double inflammatory stimulus (lipopolysaccharide [LPS] and tumour necrosis factor-alpha [TNF-α], 24 h each), and the induction of inflammation was demonstrated by (i) the increased expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and ionized calcium-binding adapter molecule 1 (IBA-1), and (ii) the increased release of interleukin 6 (IL-6) and transforming growth factor-beta (TGF-β). TRZ effects were evaluated by treating HMC3 cells for 24 h before (pre-treatment) and after (post-treatment) the double inflammatory stimulus. Notably, TRZ treatments significantly decreased the expression of NF-kB and IBA-1 and the release of the cytokines IL-6 and TGF-β. Moreover, TRZ prevented and reduced the release of quinolinic acid (QUIN), a known neurotoxic kynurenine metabolite. Finally, cellular supernatants collected from microglial cells pre-treated LPS-TNF-α with TRZ were able to improve neuronal-like cell viability, demonstrating a potential neuroprotective effect. Overall, this study suggests the anti-inflammatory effects of TRZ on human microglia and strives for its neuroprotective properties.
Insights
Trazodone (TRZ) reduces neuroinflammation in human microglia by decreasing inflammatory markers and neurotoxic quinolinic acid. This antidepressant shows potential neuroprotective effects, improving neuronal viability.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia, the brain's resident immune cells, play a crucial role in neurodevelopment and innate immunity.
- Microglial activation contributes to neuroinflammation, a key factor in brain disorders like depression.
- Antidepressants may exert therapeutic effects by modulating glial cell activity and reducing neuroinflammation.
Purpose of the Study:
- To investigate the anti-inflammatory and neuroprotective potential of trazodone (TRZ) on activated human microglial cells (HMC3).
- To assess TRZ's impact on key inflammatory mediators and neurotoxic byproducts released by microglia.
- To evaluate TRZ's ability to protect neuronal cells from microglial-induced damage.
Main Methods:
- Human microglial clone 3 (HMC3) cells were activated using a dual inflammatory stimulus (lipopolysaccharide and tumor necrosis factor-alpha).
- Trazodone (TRZ) was administered both before (pre-treatment) and after (post-treatment) the inflammatory stimulus.
- Inflammatory markers (NF-kB, IBA-1) and cytokine release (IL-6, TGF-β) were measured, alongside quinolinic acid (QUIN) levels and neuronal cell viability.
Main Results:
- TRZ treatment significantly reduced the expression of NF-kB and IBA-1 in activated microglia.
- TRZ decreased the release of pro-inflammatory cytokines IL-6 and TGF-β.
- TRZ inhibited the release of neurotoxic quinolinic acid (QUIN) and enhanced neuronal cell viability in co-culture experiments.
Conclusions:
- Trazodone exhibits significant anti-inflammatory effects on human microglia, modulating key inflammatory pathways.
- TRZ demonstrates neuroprotective properties by reducing neurotoxic factors and improving neuronal survival.
- These findings suggest trazodone's potential as a therapeutic agent for neuroinflammatory conditions, including depression.
