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- W2052060592 abstract "Epigenetic mechanisms underlying nutrition (nutrition epigenetics) are important in understanding human health. Nutritional supplements, for example folic acid, a cofactor in one-carbon metabolism, regulate epigenetic alterations and may play an important role in the maintenance of neuronal integrity. Folic acid also ameliorates hyperhomocysteinemia, which is a consequence of elevated levels of homocysteine. Hyperhomocysteinemia induces oxidative stress that may epigenetically mediate cerebrovascular remodeling and leads to neurodegeneration; however, the mechanisms behind such alterations remain unclear. Therefore, the present study was designed to observe the protective effects of folic acid against hyperhomocysteinemia-induced epigenetic and molecular alterations leading to neurotoxic cascades. To test this hypothesis, we employed 8-weeks-old male wild-type (WT) cystathionine-beta-synthase heterozygote knockout methionine-fed (CBS+/− + Met), WT, and CBS+/− + Met mice supplemented with folic acid (FA) [WT + FA and CBS+/− + Met + FA, respectively, 0.0057-μg g−1 day−1 dose in drinking water/4 weeks]. Hyperhomocysteinemia in CBS+/− + Met mouse brain was accompanied by a decrease in methylenetetrahydrofolate reductase and an increase in S-adenosylhomocysteine hydrolase expression, symptoms of oxidative stress, upregulation of DNA methyltransferases, rise in matrix metalloproteinases, a drop in the tissue inhibitors of metalloproteinases, decreased expression of tight junction proteins, increased permeability of the blood-brain barrier, neurodegeneration, and synaptotoxicity. Supplementation of folic acid to CBS+/− + Met mouse brain led to a decrease in the homocysteine level and rescued pathogenic and epigenetic alterations, showing its protective efficacy against homocysteine-induced neurotoxicity." @default.
- W2052060592 created "2016-06-24" @default.
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- W2052060592 date "2013-10-13" @default.
- W2052060592 modified "2023-10-14" @default.
- W2052060592 title "Nutri-epigenetics Ameliorates Blood–Brain Barrier Damage and Neurodegeneration in Hyperhomocysteinemia: Role of Folic Acid" @default.
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- W2052060592 doi "https://doi.org/10.1007/s12031-013-0122-5" @default.
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