Edible Folic and Folinic acid supplementation promotes myocardial cell survival and anti-apoptotic effects in Aging triple-transgenic Alzheimer's mice heart

Abstract

BackgroundCardiomyocytes undergoing apoptosis have been found in a variety of pathological conditions. Evidence suggests that Alzheimer’s disease (AD) and cardiovascular disease share some risk factors, and persons with AD have a higher risk of incident ischemic heart disease.ObjectivesThis study sought to assess the anti-apoptotic effect and survival enhancement in aged AD mice heart in response to folic acid (FA) and folinic acid (FN). Methods In this study, 16-month-old triple-transgenic (3xTg-AD; PS1M146V, APPS we and tauP301L) late-stage AD mice, were randomly allocated into three groups; AD, AD plus FA, and AD plus FN. Mice were orally fed FA or FN once daily at a dose corresponding to 1.2 mg/kg body weight (BW). After sacrifice, the excised heart tissues were processed, and morphological analyses and TUNEL assays were carried out. Further, Western blot assays were performed to quantify the amount of apoptosis and survival protein expression in the AD group compared to the FA and FS groups.ResultsResults indicated reduced intercellular space and well-maintained cardiac cell morphology in both FA- and FN-treated mouse heart tissue. These were even more pronounced in the FN-treated mice. Moreover, the AD groups had a greater number of TUNEL-positive cardiac cells than the other groups. The Western blotting results showed a greater reduction of FAS/L and C-Caspase-3 in FA-treated mice, but FADD and Caspase-8 were strongly reduced in FN-treated mice. ConclusionCollectively, our results suggest that FA or FN could inhibit heart damage by promoting cardiac cell survival and preventing apoptosis in triple-transgenic late-stage AD aging mice.