Folate Deficiency Increased Microglial Amyloid-β Phagocytosis via the RAGE Receptor in Chronic Unpredictable Mild-Stress Rat and BV2 Cells.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Alzheimer Disease* ; Folic Acid Deficiency*/complications; Animals ; Rats ; Microglia ; Amyloid beta-Peptides ; Phagocytosis ; Receptor for Advanced Glycation End Products ; Folic Acid/pharmacology

Depression is often considered one of the prevalent neuropsychiatric symptoms of Alzheimer's disease (AD). β-amyloid (Aβ) metabolism disorders and impaired microglia phagocytosis are potential pathological mechanisms between depression and AD. Folate deficiency (FD) is a risk factor for depression and AD. In this study, we used a chronic unpredictable mild stress (CUMS) rat model and a model of Aβ phagocytosis by BV2 cells to explore the potential mechanisms by which FD affects depression and AD. The results revealed that FD exacerbated depressive behavior and activated microglia in CUMS rats, leading to an increase in intracellular Aβ and phagocytosis-related receptors for advanced glycation end products (RAGE). Then, in vitro results showed that the expression of the RAGE receptor and M2 phenotype marker (CD206) were upregulated by FD treatment in BV2 cells, leading to an increase in Aβ phagocytosis. However, there was no significant difference in the expression of toll-like receptor 4 (TLR4) and clathrin heavy chain (CHC). Furthermore, when using the RAGE-specific inhibitor FPS-ZM1, there was no significant difference in Aβ uptake between folate-normal (FN) and FD BV2 cell groups. In conclusion, these findings suggest FD may promote microglia phagocytosis Aβ via regulating the expression of RAGE or microglia phenotype under Aβ treatment.

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82173516 National Natural Science Foundation of China; 2019ZD026 the Scientific Research Project of Tianjin Educational Committee

Keywords: chronic unpredictable mild stress (CUMS); folate deficiency; microglia; phagocytosis; receptor for advanced glycation end products RAGE; β-amyloid protein (Aβ)

0 (Amyloid beta-Peptides)
0 (Receptor for Advanced Glycation End Products)
935E97BOY8 (Folic Acid)

Date Created: 20230826 Date Completed: 20230828 Latest Revision: 20230829

20240829

PMC10457913

10.3390/nu15163501

37630692