Folic acid prevents habituation memory impairment and oxidative stress in an aging model induced by D-galactose
METABOLIC BRAIN DISEASE
Authors: Garcez, Michelle Lima; Cassoma, Ricardo Chiengo Sapalo; Mina, Francielle; Bellettini-Santos, Tatiani; da Luz, Aline Pereira; Schiavo, Gustavo Luis; Medeiros, Eduarda Behenck; Campos, Ana Carolina Brunatto Falchetti; da Silva, Sabrina; Rempel, Lisienny Campoli Tono; Steckert, Amanda Valnier; Barichello, Tatiana; Budni, Josiane
Abstract
The present study aimed to evaluate the effect of folic acid treatment in an animal model of aging induced by D-galactose (D-gal). For this propose, adult male Wistar rats received D-gal intraperitoneally (100 mg/kg) and/or folic acid orally (5 mg/kg, 10 mg/kg or 50 mg/kg) for 8 weeks. D-gal caused habituation memory impairment, and folic acid (10 mg/kg and 50 mg/kg) reversed this effect. However, folic acid 50 mg/kg per se caused habituation memory impairment. D-gal increased the lipid peroxidation and oxidative damage to proteins in the prefrontal cortex and hippocampus from rats. Folic acid (5 mg/kg, 10 mg/kg, or 50 mg/kg) partially reversed the oxidative damage to lipids in the hippocampus, but not in the prefrontal cortex, and reversed protein oxidative damage in the prefrontal cortex and hippocampus. D-gal induced synaptophysin and BCL-2 decrease in the hippocampus and phosphorylated tau increase in the prefrontal cortex. Folic acid was able to reverse these D-gal-related alterations in the protein content. The present study shows folic acid supplementation as an alternative during the aging to prevent cognitive impairment and brain alterations that can cause neurodegenerative diseases. However, additional studies are necessary to elucidate the effect of folic acid in aging.
FoxO1 overexpression reduces A beta production and tau phosphorylation in vitro
NEUROSCIENCE LETTERS
Authors: Zhang, Wei; Bai, Shanshan; Yang, Jianhua; Zhang, Yimin; Liu, Youcai; Nie, Junjiu; Meng, Dongli; Shi, Ruling; Yao, Zhaoyang; Wang, Mingyong; Wang, Hecheng; Li, Cuiping
Abstract
Forkhead box O1 (FoxO1), a key molecule in the regulation of cell growth, differentiation and metabolism, is an important transcription factor. However, the effect of FoxO1 on Alzheimer's disease (AD) needs further investigation. In this study, we aimed to explore the function and mechanism of FoxO1 in amyloid-beta (A beta) production and tau phosphorylation in AD. First, compared with the age matched wild-type (WT) mice, we showed that FoxO1 protein levels were reduced in the cortices but nearly unchanged in the hippocampi of 6-month-old APPswe/PSEN1dE9 transgenic mice expressing Swedish APP and Presenilin1 delta exon 9 mutations (APP/PS1 mice). Then, we found that overexpression of FoxO1 significantly attenuated A beta production through inhibiting the amyloidogenic processing of beta-amyloid precursor protein (APP), mediated by the key enzymes BACE1 and PS1, in N2a/APPsw cells. Furthermore, in FoxO1-overexpressing HEK293/Tau cells, the decreased levels of tau phosphorylation at selective sites (S262 and T231) were accompanied by increasing the expression of p-GSK-3 beta (S9), and reducing p-ERK. In contrast, the total tau (Tau-5), non-phosphorylated tau (Tau-1), p-Tau (S404), CDK5 and PP2A levels remained unchanged. These findings indicate that FoxO1 is related to AD and suggest FoxO1 as a therapeutic target for AD that reduces the levels of both A beta expression and tau phosphorylation.
COA
Publication 
 monoclonal Antibody, clone FQS3500.jpg)
 monoclonal Antibody, clone FQS3407.jpg)
 Antibody_1.gif)
Loading ......
