Microglial activation in neuroinflammation: Implications for the etiology of neurodegeneration

Background: Activated microglia secrete inflammatory cytokines and may play roles in the progression of neurodegenerative diseases. However, the mechanism underlying microglial activation remains unclear. Objective: Our aim was to examine the regulation of activated microglia through their cell death and survival pathways. Methods: We used mouse primary-cultured microglia, which are destined to die within a few days under ordinary culture conditions. The microglia live for longer than 1 month, without any measurable increase in apoptotic or necrotic cell death, when kept activated by sublethal concentrations of lipopolysaccharide (LPS). Results: LPS-treated microglia showed changes in shape. LPS treatment had no effect on the level of the proapoptotic Bcl-2-associated X protein but increased the level of the antiapoptotic protein Bcl-xL at day 1. Furthermore, the level of microtubule-associated light chain 3-II, a marker protein for autophagy, was decreased 3 h after exposure to LPS.Conclusion:An increase in Bcl-xL seems to inhibit both apoptosis and autophagy. Our results suggest that long-lived microglia resulting from exposure to the optimal dose of LPS may play critical roles in the progression of neurodegeneration.