Vitamin E induces ramification and downregulation of adhesion molecules in cultured microglial cells

Microglial cells in the healthy adult CNS possess a characteristic ramified morphology and show little or no expression of major histocompatibility complex (MHC) or adhesion molecules. In contrast, microglial cells isolated from newborn rat brains inevitably show a nonramified amoeboid morphology and express immunoeffector molecules, such as MHC class I and II, and various adhesion molecules thought to be markers of microglial activation. Furthermore, they produce large amounts of oxygen radicals. Treatment of cultured microglial cells with the antioxidants vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid) induced a ramified microglial morphology after 48 h in vitro, otherwise only seen in healthy adult CNS tissue or in co-culture with astrocytes. Morphological transformation of microglial cells was quantified by morphometric analysis and was found to be statistically significant. Ramification of microglia induced by vitamin E was accompanied by downregulated expression of adhesion molecules leukocyte function antigen-1, very late antigen-4, and intercellular adhesion molecule-1, as assessed by FACS analysis and immunocytochemistry. Moreover, cell numbers of microglia treated with vitamin E remained stable within 7 days in vitro, whereas untreated controls showed a cell loss of 81.5%. These data show that vitamin E acts as a protective compound in dissociated microglial cell cultures. In conclusion, our results suggest that vitamin E and vitamin C shift microglial morphology toward ramification and induce an immunological deactivation. These changes seem to be mediated by oxidative mechanisms.