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

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.788723

DOI=10.3389/fnagi.2021.788723

ISSN=1663-4365

ABSTRACT=<p><bold>Background and objectives:</bold> This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oAβ)<sub>1–42</sub> in BV-2 mouse microglial cells.</p><p><bold>Methods:</bold> An <italic>in vitro</italic> model was established to investigate phagocytosis of oAβ<sub>1–42</sub> in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oAβ<sub>1–42</sub> was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oAβ<sub>1–42</sub> (FAM-oAβ<sub>1–42</sub>) for 24 h, followed by flow cytometer analysis, western blotting, real-time quantitative PCR, and immunocytochemistry (ICC) analysis to assess the <italic>in vitro</italic> phagocytosis ability of oAβ<sub>1–42</sub>.</p><p><bold>Results:</bold> 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<sub>1–42</sub> treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oAβ<sub>1–42</sub> 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-<sup>Δ12,14</sup>-prostaglandin J2 in BV-2 cells.</p><p><bold>Conclusion:</bold> We postulated that ALA enhances oAβ<sub>1–42</sub> phagocytosis by upregulating the COX-2/15-deoxy-<sup>Δ12,14</sup>-prostaglandin J2/PPAR-γ/CD36 pathway in BV-2 cells. Finally, future studies should be conducted with an <italic>in vivo</italic> study to confirm the findings.</p>