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Updated: Mar 24, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Anthocyanin effects on microglia M1/M2 phenotype: Consequence on neuronal fractalkine expression
Manuela Meireles1, Cláudia Marques1, Sónia Norberto1
1Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; CINTESIS-Center for Research in Health Technologies and Information Systems, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
Abstract:
Microglia mediate multiple aspects of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype or microglia-neuron crosstalk can be an appealing neurotherapeutic strategy. Anthocyanins are a class of flavonoids found e.g., in berries that has been attracting interest due to its neuroprotective potential. However, there are no data clarifying the impact of anthocyanins on microglial phenotype or on microglia-neuron crosstalk (CX3CR1/CX3CL1). N9 microglia cell line was treated with 1μM cyanidin (Cy), cyanidin-3-glucose (Cy3glc) and a methylated form of cyanidin-3-glucose (Met-Cy3glc) in basal conditions and with LPS/IL-4 stimulation. SH-SY5Y cell line was treated with the conditioned medium of microglia and with the anthocyanins alone. At basal conditions, microglia treatment with anthocyanins for 24h induced a less pro-inflammatory profile. Decreased TNF-α mRNA expression was induced either by Cy and Met-Cy3glc. LPS markedly increase IL-6 mRNA expression, which was lowered by Cy3glc. IL-1β LPS-induced expression was reverted by Cy. Cy increased CX3CL1 mRNA expression in SH-SY5Y comparing either with control or LPS. Anthocyanins and metabolites were not able to shift microglia to an M2 strict phenotype however they did interact with microglia biology. There was an attenuation of M1 phenotype and increase of neuronal expression of CX3CL1 mRNA. Understanding how flavonoids modulate microglia-neuron crosstalk can open new directions for future nutritional interventions.
Insights
Anthocyanins, found in berries, may offer neuroprotection by modulating microglial phenotype and reducing neuroinflammation. These flavonoids interact with microglia biology, potentially influencing microglia-neuron crosstalk for therapeutic benefit.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia are key players in neuroinflammation, exhibiting diverse activation states.
- Modulating microglial phenotype and microglia-neuron crosstalk presents a potential neurotherapeutic strategy.
- Anthocyanins, berry-derived flavonoids, show promise for neuroprotection, but their effects on microglia are unclear.
Purpose of the Study:
- To investigate the impact of anthocyanins (cyanidin, cyanidin-3-glucose, methylated cyanidin-3-glucose) on microglial phenotype and microglia-neuron crosstalk.
- To assess anthocyanin effects on inflammatory markers and CX3CL1 expression in microglia and neuronal cell lines.
Main Methods:
- N9 microglia and SH-SY5Y neuronal cell lines were treated with anthocyanins under basal and stimulated (LPS/IL-4) conditions.
- Analysis included mRNA expression of inflammatory cytokines (TNF-α, IL-6, IL-1β) and CX3CL1.
- Conditioned media from treated microglia were used to assess effects on SH-SY5Y cells.
Main Results:
- Anthocyanins induced a less pro-inflammatory microglial profile at basal conditions.
- Cyanidin and methylated cyanidin-3-glucose decreased TNF-α mRNA expression.
- Cyanidin-3-glucose lowered LPS-induced IL-6 expression, while cyanidin reverted IL-1β expression.
- Cyanidin increased CX3CL1 mRNA expression in SH-SY5Y cells, suggesting modulation of microglia-neuron crosstalk.
Conclusions:
- Anthocyanins interact with microglia biology, attenuating the M1 pro-inflammatory phenotype.
- While not inducing a strict M2 phenotype, anthocyanins influenced microglia-neuron crosstalk by increasing neuronal CX3CL1 expression.
- These findings suggest potential for nutritional interventions targeting neuroinflammation and microglia-neuron communication.
