Lack of Alpha-Synuclein Modulates Microglial Phenotype In Vitro

Alpha (alpha)-synuclein neuronal effects are continually being defined although its role in regulating glial phenotypes remains unclear. An ability to regulate microglial activation was investigated using primary cultures from wild type and alpha-synuclein deficient mice (Snca (-/-)). Snca (-/-) microglia demonstrated increased secretion of the cytokine tumor necrosis factor-alpha (TNF-alpha), impaired phagocytic ability, elevated prostaglandin levels, and increased protein levels of key enzymes in lipid-mediated signaling events, cytosolic phospholipase (cPLA(2)), cyclooxygenase-2 (Cox-2) and phospholipase D2 (PLD2) when compared to wild type cells. Increased cytokine secretion and cPLA(2) and Cox-2 levels in Snca (-/-) microglia were partially attenuated by inhibiting PLD-dependent signaling with n-butanol treatment.