Dendritic polyglycerols are modulators of microglia-astrocyte crosstalk

To determine the ability of sulfated dendritic polyglycerols (dPGS) to modulate neuroglia activation challenged with lipopolysaccharide (LPS). Materials & methods: Microglia/astrocyte activation in vivo was determined in transgenic animals expressing TLR2-/GFAP-luciferase reporter. Mechanisms implicated in microglia-astrocyte crosstalk were studied in primary mouse brain cultures. Results & discussion: dPGS significantly reduced microglia activation in vivo, and decreased astrocytic LCN2 production. Activated microglia are necessary for astrocyte stimulation and increase in LCN2 abundance. LCN2 production in astrocytes involves signaling via toll-like receptor 4, activation of NF-kappa B, IL6 and enhancement of reactive oxygen species. Conclusion: dPGS are powerful modulators of microglia-astrocyte crosstalk and LCN2 abundance; dPGS are promising anti-inflammatory dendritic nanostructures. [GRAPHICS] . Lay abstract: We investigated dendritic polymer effects on brain glial cells: microglia and astrocytes. Microglia are immune cells of the CNS that modulate the activity of astrocytes and production of destructive or protective proteins, including lipocalin-2. We tested dendritic polymers with sulfate terminal groups in both animal models and cultured primary brain cells. We show that a sulfate end group is necessary for polyglycerol dendrimers to exert anti-inflammatory activity and reduce lipocalin-2 production in astrocytes. Sulfated dendritic polyglycerols merit investigations as nanotherapeutics in neurodegenerative disorders associated with inflammation in the brain.