Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression.
Recent efforts have revealed the microRNA (miRNA) pathways in the pathogenesis of Alzheimer's disease (AD). Epidemiological studies have revealed an association between folic acid deficiency and AD risk. However, the effects of folic acid deficiency on miRNA expression in AD animals have not been observed. We aimed to find if folic acid deficiency may enhance amyloid-β (Aβ) peptide deposition and regulate amyloid-associated miRNAs and their target genes expression in APP/PS1 mice. APP/PS1 mice and N2a cells were treated with folic acid-deficient diet or medium. Cognitive function of mice was assessed using the Morris water maze. miRNA profile was tested by polymerase chain reaction (PCR) array. Different expressional miRNAs were validated by real-time PCR. The deposition of Aβ plaques was evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. APP and BACE1 proteins in mice brain and N2a cells were determined by Western blot. Folic acid deficiency aggravated amyloid pathology in AD mice. The AD+FD group showed shorter time spent in the target zone during the probe test. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that were differentially modulated by folic acid deficiency. In APP/PS1 mice brains and N2a cells with folic acid-deficient treatment, miR-106a-5p, miR-200b-3p and miR-339-5p were down-regulated, and their target genes APP and BACE1 were up-regulated. In conclusion, folic acid deficiency can enhance Aβ accumulation in APP/PS1 mice brain and decrease amyloid-associated miRNAs expression.
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Huan
H
Liu
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Tian
T
Tian
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Shanchun
S
Qin
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Wen
W
Li
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Xumei
X
Zhang
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Xuan
X
Wang
Department of Cardiology, General Hospital of Tianjin Medical University, Tianjin 300152, China.
Yuxia
Y
Gao
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China. Electronic address: huangguowei@tmu.edu.cn.
Guowei
G
Huang
D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D003071:Cognition; D003072:Cognition Disorders / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005492:Folic Acid / Q000097:blood / Q000737:chemistry*; D005494:Folic Acid Deficiency / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D053764:Presenilin-1 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D035683:MicroRNAs; D053764:Presenilin-1; D005492:Folic Acid; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
APP/PS1 mice; Alzheimer's disease; Amyloid β-peptide; Folic acid; MicroRNA