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Folic Acid and Folinic Acid Protect Hearts of Aging Triple-transgenic Alzheimer’s Disease mice via IGF1R/PI3K/AKT and SIRT1/AMPK Pathways
Neurotoxicity Research ( IF 3.7 ) Pub Date : 2023-09-14 , DOI: 10.1007/s12640-023-00666-z
Da-Tong Ju, Rwei-Fen S. Huang, Bruce Chi-Kang Tsai, Yi-Chen Su, Ping-Ling Chiu, Yung-Ming Chang, V. Vijaya Padma, Tsung-Jung Ho, Chun-Hsu Yao, Wei-Wen Kuo, Chih-Yang Huang

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.



中文翻译:

叶酸和亚叶酸通过 IGF1R/PI3K/AKT 和 SIRT1/AMPK 途径保护衰老三转基因阿尔茨海默病小鼠的心脏

阿尔茨海默病患者患心脏病的风险增加,因此强调需要制定旨在减少阿尔茨海默病相关心血管疾病的策略。叶酸和亚叶酸对心脏有益。我们的目的是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个月大的三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、阿尔茨海默病+亚叶酸组。给小鼠口服叶酸或亚叶酸12 mg/kg,每日一次,持续3个月。与阿尔茨海默病组相比,叶酸和亚叶酸治疗组的细胞间隙减小。TUNEL检测和蛋白质印迹图像显示,阿尔茨海默病组的凋亡细胞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,叶酸和亚叶酸治疗可增加存活率和 SIRT1 表达,从而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,叶酸和亚叶酸可促进心肌细胞存活并防止细胞凋亡,从而抑制患有三转基因晚期阿尔茨海默病的衰老小鼠的心脏损伤。特别是亚叶酸比叶酸具有更好的疗效。

更新日期:2023-09-14
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