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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 A\u03b2 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 A\u03b2 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 A\u03b2 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 A\u03b2 uptake between folate-normal (FN) and FD BV2 cell groups. In conclusion, these findings suggest FD may promote microglia phagocytosis A\u03b2 via regulating the expression of RAGE or microglia phenotype under A\u03b2 treatment.<\/jats:p>","DOI":"10.3390\/nu15163501","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:38:59Z","timestamp":1691498339000},"page":"3501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Folate Deficiency Increased Microglial Amyloid-\u03b2 Phagocytosis via the RAGE Receptor in Chronic Unpredictable Mild-Stress Rat and BV2 Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Junting","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zewei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/0278-5846(86)90051-5","article-title":"Validation criteria for animal models of human mental disorders: Learned helplessness as a paradigm case","volume":"10","author":"Willner","year":"1986","journal-title":"Prog. 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