title: Folic acid attenuates the effects of amyloid β oligomers on DNA methylation in neuronal cells.
abstract: OBJECTIVE
  Alzheimer's disease (AD) is a highly prevalent type of dementia. The epigenetic mechanism of gene methylation provides a putative link between nutrition, one-carbon metabolism, and disease progression because folate deficiency may cause hypomethylation of promoter regions in AD-relevant genes. We hypothesized that folic acid supplementation may protect neuron cells from amyloid β (Aβ) oligomer-induced toxicity by modulating DNA methylation of APP and PS1 in AD models.
  
  
  METHODS
  Primary hippocampal neuronal cells and hippocampal HT-22 cells were incubated for 24 h with a combination of folic acid and either Aβ oligomers or vehicle and were then incubated for 72 h with various concentrations of folic acid. AD transgenic mice were fed either folate-deficient or control diets and gavaged daily with various doses of folic acid (0 or 600 μg/kg). DNA methyltransferase (DNMT) activity, cell viability, methylation potential of cells, APP and PS1 expression, and the methylation of the respective promoters were determined.
  
  
  RESULTS
  Aβ oligomers lowered DNMT activity, increased PS1 and APP expression, and decreased cell viability. Folic acid dose-dependently stimulated methylation potential and DNMT activity, altered PS1 and APP promoter methylation, decreased PS1 and APP expression, and partially preserved cell viability. Folic acid increased PS1 and APP promoter methylation in AD transgenic mice.
  
  
  CONCLUSIONS
  These results suggest a mechanism by which folic acid may prevent Aβ oligomer-induced neuronal toxicity.
authors.affiliation: Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
authors.forename: Shijing
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
authors.forename: Xumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
authors.forename: John X
authors.initials: JX
authors.lastname: Wilson
authors.affiliation: Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China. tjgwhuang@126.com.
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000097:blood; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D016229:Amyloid beta-Peptides; D053764:Presenilin-1; C580804:presenilin 1, mouse; D005492:Folic Acid
keywords: APP; Alzheimer’s disease; Aβ oligomer; Folic acid; Methylation; PS1