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叶酸在体内和体外均可抑制衰老诱导的星形胶质细胞端粒磨损和凋亡。

Folic Acid Inhibits Aging-Induced Telomere Attrition and Apoptosis in Astrocytes In Vivo and In Vitro.

作者信息

Li Zhenshu, Zhou Dezheng, Zhang Dalong, Zhao Jing, Li Wen, Sun Yue, Chen Yongjie, Liu Huan, Wilson John X, Qian Zhiyong, Huang Guowei

机构信息

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China.

Department of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China.

出版信息

Cereb Cortex. 2022 Jan 10;32(2):286-297. doi: 10.1093/cercor/bhab208.

Abstract

Folic acid (FA) has been reported to inhibit astrocyte apoptosis and improve aging-induced disorders; however, its role in telomere attrition remains unclear. In present study, 4-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were assigned to four treatment groups for the in vivo experiment: FA-deficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group, and high FA-supplemented diet (FA-H) group. These mice were euthanized when 10 months old. There was also a young SAMP8 (4 months old) control group (Con-Y) fed with FA-normal diet. In in vitro study, primary cultures of astrocytes from hippocampus and cerebral cortex were incubated for five generations with various concentrations of FA (0-40 μM) and were assigned to five groups: FA 0 μM (generation 5), FA 10 μM (generation 5), FA 20 μM (generation 5), FA 40 μM (generation 5), and FA 10 μM (generation 1). The results showed that FA supplementation inhibited aging-induced astrocytosis, astrocyte apoptosis, neurodegeneration, and prevented telomere attrition in hippocampus and cortex of SAMP8 mice. FA supplementation also decreased apoptosis and telomere attrition, and increased telomerase activity, in primary cultures of astrocytes. These results showed that it may be one of the mechanisms that FA inhibiting aging-induced apoptosis of astrocyte by alleviating telomere attrition.

摘要

据报道,叶酸(FA)可抑制星形胶质细胞凋亡并改善衰老引起的紊乱;然而,其在端粒损耗中的作用仍不清楚。在本研究中,将4个月大的衰老加速小鼠8型(SAMP8)小鼠分为四个治疗组进行体内实验:叶酸缺乏饮食(FA-D)组、叶酸正常饮食(FA-N)组、低叶酸补充饮食(FA-L)组和高叶酸补充饮食(FA-H)组。这些小鼠在10个月大时实施安乐死。还有一个年轻的SAMP8(4个月大)对照组(Con-Y),给予叶酸正常饮食。在体外研究中,将来自海马体和大脑皮层的星形胶质细胞原代培养物用不同浓度的叶酸(0-40μM)培养五代,并分为五组:叶酸0μM(第5代)、叶酸10μM(第5代)、叶酸20μM(第5代)、叶酸40μM(第5代)和叶酸10μM(第1代)。结果表明,补充叶酸可抑制衰老诱导的星形胶质细胞增多、星形胶质细胞凋亡、神经退行性变,并防止SAMP8小鼠海马体和皮层中的端粒损耗。在星形胶质细胞原代培养物中,补充叶酸还可减少细胞凋亡和端粒损耗,并增加端粒酶活性。这些结果表明,叶酸可能通过减轻端粒损耗来抑制衰老诱导的星形胶质细胞凋亡,这可能是其作用机制之一。

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