Abstract
Patients with Alzheimer's disease have increased risk of developing heart disease, which therefore highlights the need for strategies aiming at reducing Alzheimer's disease-related cardiovascular disease. Folic acid and folinic acid are beneficial to the heart. We aimed to investigate the benefits of folic acid and folinic acid in heart of patients with late-stage Alzheimer's disease. Twelve 16-month-old mice of triple-transgenic late-stage Alzheimer's disease were divided into three groups: Alzheimer's disease group, Alzheimer's disease + folic acid group, and Alzheimer's disease + folinic acid group. The mice were administered 12 mg/kg folic acid or folinic acid once daily via oral gavage for 3 months. In the folic acid and folinic acid treatment groups, the intercellular space was reduced, compared with the Alzheimer's disease group. TUNEL assay and western blot images showed that the number of apoptotic cells and the apoptosis-related protein expression were higher in the Alzheimer's disease group than in other two treated groups. Folic acid and folinic acid induced the IGF1R/PI3K/AKT and SIRT1/ AMPK pathways in the hearts of mice with Alzheimer's disease. Our results showed that folic acid and folinic acid treatment increased survival and SIRT1 expression to reduce apoptotic proteins in the heart. The aging mice treated with folinic acid had more IGF1R and SIRT1/AMPK axes to limit myocardial cell apoptosis. In conclusion, folic acid and folinic acid promote cardiac cell survival and prevent apoptosis to inhibit heart damage in aging mice with triple-transgenic late-stage Alzheimer's disease. In particular, folinic acid provides a better curative effect than folic acid.
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Abbreviations
- DDW:
-
Double distilled water
- H&E:
-
Hematoxylin and eosin
- TUNEL:
-
Terminal deoxynucleotidyl Transferase (TdT)-mediated dUTP-biotin nick end labeling
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Funding
This study was supported by a study project grant from Tri-Service General Hospital, China Medical University, China Medical University Hospital, Hualien Tzu Chi Hospital (TSGH-D-110073, TSGH-D-111089, TSGH-D-112096, CMU-109-S-20, DMR-109-163, and IMAR-110-01-15), and National Science and Technology Council (Taiwan, NSTC 111-2811-B-303-006).
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Chih-Yang Huang and Da-Tong Ju: Conceptualization, Methodology, Validation, Formal analysis, Writing - review & editing, Investigation, and Financial support. Rwei-Fen S Huang: Data curation, Writing - original draft, Writing - review & editing. Bruce Chi-Kang Tsai: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, and Writing - original draft. Yi-Chen Su and Ping-Ling Chiu: Investigation, Writing - original draft, and Writing - re-view & editing. Yung-Ming Chang and V. Vijaya Padma: Writing - review & editing and Validation. Tsung-Jung Ho: Writing - review & editing. Wei-Wen Kuo and Chun-Hsu Yao: Provide materials and Financial support Wei-Wen Kuo and Da-Tong Ju: Project administration, Conceptualization, and Methodology.
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Highlights
1. Folic acid and Folinic acid promote cardiac cell survival in AD aging mice.
2. Folic acid and Folinic acid prevent cardiomyocytes apoptosis in AD aging mice.
3. Folic acid and Folinic acid inhibit heart damage through SIRT-1 signaling pathway.
4. Folic acid and Folinic acid maintain heart via IGF1R/PI3K/AKT signaling pathway.
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Ju, DT., Huang, RF.S., Tsai, B.CK. et al. Folic Acid and Folinic Acid Protect Hearts of Aging Triple-transgenic Alzheimer’s Disease mice via IGF1R/PI3K/AKT and SIRT1/AMPK Pathways. Neurotox Res 41, 648–659 (2023). https://doi.org/10.1007/s12640-023-00666-z
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DOI: https://doi.org/10.1007/s12640-023-00666-z