Effects of α-Lipoic Acid on Phagocytosis of Oligomeric Beta-Amyloid1-42 in BV-2 Mouse Microglial Cells

Chih-Yuan Ko; Jian-Hua Xu; Yu-Wei Chang; Yangming Martin Lo; James Swi-Bea Wu; Wen-Chung Huang; Szu-Chuan Shen

doi:10.3389/fnagi.2021.788723

Effects of α-Lipoic Acid on Phagocytosis of Oligomeric Beta-Amyloid_1-42 in BV-2 Mouse Microglial Cells

Front Aging Neurosci. 2022 Jan 12:13:788723. doi: 10.3389/fnagi.2021.788723. eCollection 2021.

Authors

Chih-Yuan Ko^{1

2

3

4}, Jian-Hua Xu⁵, Yu-Wei Chang⁶, Yangming Martin Lo⁷, James Swi-Bea Wu⁸, Wen-Chung Huang⁹, Szu-Chuan Shen⁶

Affiliations

¹ Department of Clinical Nutrition, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
² Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
³ School of Public Health, Fujian Medical University, Fuzhou, China.
⁴ Respiratory Medicine Center of Fujian Province, Quanzhou, China.
⁵ Department of Tumor Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
⁶ Graduate Program of Nutrition Science, National Taiwan Normal University, Taipei, Taiwan.
⁷ Institute for Advanced Study, Shenzhen University, Shenzhen, China.
⁸ Graduate Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
⁹ Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.

Abstract

Background and objectives: This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oAβ)_1-42 in BV-2 mouse microglial cells. Methods: An in vitro model was established to investigate phagocytosis of oAβ_1-42 in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oAβ_1-42 was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oAβ_1-42 (FAM-oAβ_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 oAβ_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 oAβ_1-42 treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oAβ_1-42 in BV-2 cells. Moreover, ICC analysis revealed that ALA caused the translocation of peroxisome proliferator-activated receptor-γ (PPAR-γ), 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-^Δ12,14-prostaglandin J2 in BV-2 cells. Conclusion: We postulated that ALA enhances oAβ_1-42 phagocytosis by upregulating the COX-2/15-deoxy-^Δ12,14-prostaglandin J2/PPAR-γ/CD36 pathway in BV-2 cells. Finally, future studies should be conducted with an in vivo study to confirm the findings.

Keywords: Alzheimer’s disease (AD); microglia; oligomeric beta-amyloid; phagocytosis; α-lipoic acid.