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Supplementation of aging transgenic mice with folic acid and folinic acid alleviates Alzheimer's disease‐associated neuronal amyloid‐β (Aβ) pathological progression and genomic expression profiles
Author(s) -
Chen TaFu,
Hsu HungCheng,
Chiu MingJang,
S. Huang RweiFen
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.919.3
Subject(s) - alzheimer's disease , genetically modified mouse , hippocampus , medicine , endocrinology , folinic acid , amyloid precursor protein , biology , transgene , biochemistry , gene , disease , cancer , colorectal cancer
Aims of the study are to investigate whether and the molecular mechanisms by which supplementation of folic acid (FA) and folinic acid (FN) may ameliorate late‐stage Alzheimer's disease (AD)‐associated pathological development using the 3xTg transgenic mice as the experimental model. Forty 3xTg‐AD mice at 16 month‐old were divided into three groups fed with the AIN93M diet in the absence (Control) or presence of FA and FN supplements (12 mg/kg/day by force feeding) for 3 months. The amyloid‐β (Aβ) levles were measured by immunoblotting. Genomic expression profiles of hippocampus of mice were assayed by cDNA microarray. As compared with the controls, FA and FN groups had significantly reduced brain Aβ40, Aβ42 or pTau levels. Pearson's analysis revealed the significant and inverse associations of brain Aβ40, Aβ42 and pS199 tau with serum folate levels. FN treatment significantly modified expression profiles of AD‐hippocampus genes associated with olfactory transduction, complement and coagulation cascades, and neuroactive ligand‐receptor interaction, whereas FA‐modified AD gene expression overlapped in complement and coagulation cascades. Survival rates of FA and FN groups was 1.6 fold‐increased in relative to the controls at 19 month‐old. The data demonstrated that FA and FN treatments may alleviate pathological severity of late‐stage AD associated with increased survival rate of 3xTg‐AD mice.