Edible folic acid and medicinal folinic acid produce cardioprotective effects in late-stage triple-transgenic Alzheimer's disease model mice by suppressing cardiac hypertrophy and fibrosis

Chih Yang Huang, Yi Chen Su, Cheng You Lu, Ping Ling Chiu, Yung Ming Chang, Da Tong Ju, Ray Jade Chen, Liang Yo Yang, Tsung Jung Ho, Hui Chuan Kao

Research output: Contribution to journalArticlepeer-review

Abstract

Some clinical studies have indicated the patients with Alzheimer's disease (AD) display an increased risk of cardiovascular disease (CVD). Here, to examine the relationship between AD and CVDs, we investigated the changes in heart function in triple-transgenic late-stage AD model mice (3× Tg-AD; APPSwe, PS1M146V, and tauP301L). We fed the AD mice folic acid (FA) or folinic acid (FN) and analyzed the protective effects of the compounds on the heart; specifically, 20-month-old triple-transgenic AD mice, weighing 34–55 g, were randomly allocated into three groups—the AD, AD + FA, and AD + FN groups—and subject to gastric feeding with FA or FN once daily at 12 mg/kg body weight (BW) for 3 months. Mouse BWs were assessed throughout the trial, at the end of which the animals were sacrificed using carbon dioxide suffocation. We found that BW, whole-heart weight, and left-ventricle weight were reduced in the AD + FA and AD + FN groups as compared with the measurements in the AD group. Furthermore, western blotting of excised heart tissue revealed that the levels of the hypertrophy-related protein markers phospho(p)-p38 and p-c-Jun were markedly decreased in the AD + FA group, whereas p-GATA4, and ANP were strongly reduced in the AD + FN group. Moreover, the fibrosis-related proteins uPA, MMP-2, MEK1/2 and SP-1 were decreased in the heart in both AD + FN group. In summary, our results indicate that FA and FN can exert anti-cardiac hypertrophy and fibrosis effects to protect the heart in aged triple-transgenic AD model mice, particular in FN.

Original languageEnglish
Pages (from-to)1740-1749
Number of pages10
JournalEnvironmental Toxicology
Volume37
Issue number7
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • Alzheimer's disease
  • cardiac fibrosis
  • cardiac hypertrophy
  • folic acid
  • folinic acid

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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