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艾灸对APP/PS1小鼠学习记忆及m6A RNA甲基化的影响

The Effects of Moxibustion on Learning and Memory and m6A RNA Methylation in APP/PS1 Mice.

作者信息

Huang Qin, Li Chen-Yu, Zhang Ning, Zhang Qun, Li Hong-Ying, Shen Yuan, Xie Lu-Shuang, Yu Shu-Guang, Wu Qiao-Feng

机构信息

Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

出版信息

Evid Based Complement Alternat Med. 2022 Mar 21;2022:2998301. doi: 10.1155/2022/2998301. eCollection 2022.

DOI:10.1155/2022/2998301
PMID:35356237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8959951/
Abstract

OBJECTIVES

To study whether moxibustion can improve the learning and memory ability of APP/PS1 mice by reducing the pathological products A and Tau protein via decreasing N6-methyladenosine (m6A).

METHODS

APP/PS1 mice were randomly divided into model group (APP/PS1) and moxibustion group (APP/PS1+Mox). C57BL/6J mice were used as a control group (Control). Learning and memory abilities were assessed by the Morris water maze. A, Tau, phosphorylated Tau (p-Tau), and YTHDF1 proteins were detected in the mouse cortex and hippocampus by immunofluorescence and western blot. Altered m6A expression levels in hippocampal and cortical tissues were measured with the m6A RNA methylation quantification assay kit. RNA transcript levels of YTHDF1, METTL3, and FTO in the hippocampus and cortex were measured by q-PCR.

RESULTS

Moxibustion shortened the escape latency, increased the number of platform crossings, and increased the percentage of swimming time in the target quadrant of APP/PS1 mice. Meanwhile, moxibustion reduced the levels of A, Tau, and p-Tau proteins both in the hippocampal and cortical regions of APP/PS1 mice. In addition, the total amount of m6A in the hippocampal and cortical regions of APP/PS1 mice was significantly reduced after moxibustion. The expression of YTHDF1 in the hippocampal region of APP/PS1 mice increased and that in the cortical region decreased after moxibustion treatment.

CONCLUSION

Moxibustion improves the learning and memory abilities and reduces the deposition of A and Tau protein pathological products in APP/PS1 mice. This may be related to the fact that moxibustion reduces the total amount of m6A and inhibits its binding enzyme YTHDF1 in the hippocampus and cortex of APP/PS1 mice.

摘要

目的

研究艾灸是否可通过降低N6-甲基腺苷(m6A)减少病理产物A和 Tau蛋白,从而改善APP/PS1小鼠的学习记忆能力。

方法

将APP/PS1小鼠随机分为模型组(APP/PS1)和艾灸组(APP/PS1+Mox)。将C57BL/6J小鼠作为对照组(Control)。通过Morris水迷宫评估学习记忆能力。采用免疫荧光和蛋白质印迹法检测小鼠皮质和海马中A、Tau、磷酸化Tau(p-Tau)和YTHDF1蛋白。使用m6A RNA甲基化定量检测试剂盒测量海马和皮质组织中m6A表达水平的变化。通过q-PCR测量海马和皮质中YTHDF1、METTL3和FTO的RNA转录水平。

结果

艾灸缩短了APP/PS1小鼠的逃避潜伏期,增加了穿越平台的次数,并增加了目标象限游泳时间的百分比。同时,艾灸降低了APP/PS1小鼠海马和皮质区域中A、Tau和p-Tau蛋白的水平。此外,艾灸后APP/PS1小鼠海马和皮质区域中m6A的总量显著降低。艾灸处理后,APP/PS1小鼠海马区域中YTHDF1的表达增加,皮质区域中YTHDF1的表达降低。

结论

艾灸可改善APP/PS1小鼠的学习记忆能力,并减少A和Tau蛋白病理产物的沉积。这可能与艾灸降低APP/PS1小鼠海马和皮质中m6A的总量并抑制其结合酶YTHDF1有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/5c39813096dc/ECAM2022-2998301.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/ad8bd17ba272/ECAM2022-2998301.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/56cdcb4eec72/ECAM2022-2998301.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/fe74ef66f26a/ECAM2022-2998301.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/0cbac06fa707/ECAM2022-2998301.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/da08ce2e51c3/ECAM2022-2998301.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/5c39813096dc/ECAM2022-2998301.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/ad8bd17ba272/ECAM2022-2998301.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/56cdcb4eec72/ECAM2022-2998301.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/fe74ef66f26a/ECAM2022-2998301.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/0cbac06fa707/ECAM2022-2998301.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/da08ce2e51c3/ECAM2022-2998301.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c74a/8959951/5c39813096dc/ECAM2022-2998301.006.jpg

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