Effects of alpha-Lipoic Acid on Phagocytosis of Oligomeric Beta-Amyloid(1-42) in BV-2 Mouse Microglial Cells

Background and objectives: This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oA beta)(1-42) in BV-2 mouse microglial cells.Methods: An in vitro model was established to investigate phagocytosis of oA beta(1-42) in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oA beta(1-42) was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oA beta(1-42) (FAM-oA beta(1-42)) for 24 h, followed by flow cytometer analysis, western blotting, real-time quantitative PCR, and immunocytochemistry (ICC) analysis to assess the in vitro phagocytosis ability of oA beta(1-42).Results: Alpha-lipoic acid significantly increased messenger RNA (mRNA) expression of the CD36 receptor in BV-2 cells. ICC analysis showed that ALA significantly elevated CD36 protein expression in BV-2 cells both with and without oA beta(1-42) treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oA beta(1-42) in BV-2 cells. Moreover, ICC analysis revealed that ALA caused the translocation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which is known to regulate the expression of CD36 mRNA in BV-2 cells. ALA also elevated both the mRNA and protein expression of cyclooxygenase-2 (COX-2), which is a key enzyme involved in the synthesis of 15-deoxy-(& UDelta;12,14)-prostaglandin J2 in BV-2 cells.Conclusion: We postulated that ALA enhances oA beta(1-42) phagocytosis by upregulating the COX-2/15-deoxy-(& UDelta;12,14)-prostaglandin J2/PPAR-gamma/CD36 pathway in BV-2 cells. Finally, future studies should be conducted with an in vivo study to confirm the findings.