Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Graduate Institute of Nutrition and Food Science, Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan.
Neurotox Res. 2023 Dec;41(6):648-659. doi: 10.1007/s12640-023-00666-z. Epub 2023 Sep 14.
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.
阿尔茨海默病患者患心脏病的风险增加，因此需要制定旨在降低与阿尔茨海默病相关的心血管疾病风险的策略。叶酸和亚叶酸对心脏有益。我们旨在研究叶酸和亚叶酸对晚期阿尔茨海默病患者心脏的益处。将 12 只 16 月龄的三重转基因晚期阿尔茨海默病小鼠分为三组：阿尔茨海默病组、阿尔茨海默病+叶酸组和阿尔茨海默病+亚叶酸组。通过口服灌胃每天给予小鼠 12mg/kg 叶酸或亚叶酸，持续 3 个月。与阿尔茨海默病组相比，在叶酸和亚叶酸治疗组中，细胞间隙减少。TUNEL 检测和 Western blot 图像显示，阿尔茨海默病组的细胞凋亡数量和凋亡相关蛋白表达高于其他两个治疗组。叶酸和亚叶酸诱导了阿尔茨海默病小鼠心脏中的 IGF1R/PI3K/AKT 和 SIRT1/AMPK 通路。我们的结果表明，叶酸和亚叶酸治疗增加了存活并提高了 SIRT1 表达，以减少心脏中的凋亡蛋白。用亚叶酸治疗的衰老小鼠具有更多的 IGF1R 和 SIRT1/AMPK 轴，以限制心肌细胞凋亡。总之，叶酸和亚叶酸促进心脏细胞存活并预防凋亡，从而抑制三重转基因晚期阿尔茨海默病衰老小鼠的心脏损伤。特别是，亚叶酸比叶酸提供更好的疗效。
