18 kDa Translocator Protein TSPO Is a Mediator of Astrocyte Reactivity

An increase in astrocytereactivity has been described in Alzheimer'sdisease and seems to be related to the presence of a pro-inflammatoryenvironment. Reactive astrocytes show an increase in the density ofthe 18 kDa translocator protein (TSPO), but TSPO involvement in astrocytefunctions remains poorly understood. The goal of this study was tobetter characterize the mechanisms leading to the increase in TSPOunder inflammatory conditions and the associated consequences. Forthis purpose, the C6 astrocytic cell line was used in the presenceof lipopolysaccharide (LPS) or TSPO overexpression mediated by thetransfection of a plasmid encoding TSPO. The results show that nonlethaldoses of LPS induced TSPO expression at mRNA and protein levels througha STAT3-dependent mechanism and increased the number of mitochondriaper cell. LPS stimulated reactive oxygen species (ROS) productionand decreased glucose consumption (quantified by the [F-18]FDG uptake), and these effects were diminished by FEPPA, a TSPOantagonist. The transfection-mediated overexpression of TSPO inducedROS production, and this effect was blocked by FEPPA. In addition,a synergistic effect of overexpression of TSPO and LPS on ROS productionwas observed. These data show that the increase of TSPO in astrocyticcells is involved in the regulation of glucose metabolism and in thepro-inflammatory response. These data suggest that the overexpressionof TSPO by astrocytes in Alzheimer's disease would have ratherdeleterious effects by promoting the pro-inflammatory response.