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Updated: Sep 28, 2025
Analysis of Learning and Memory Ability in an Alzheimer's Disease Mouse Model using the Morris Water Maze
Published on: October 29, 2019
The Effects of Moxibustion on Learning and Memory and m6A RNA Methylation in APP/PS1 Mice
Qin Huang1, Chen-Yu Li1, Ning Zhang1
1Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Objectives:
To study whether moxibustion can improve the learning and memory ability of APP/PS1 mice by reducing the pathological products Aβ 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. Aβ, 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 Aβ, 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 Aβ 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.
Insights
Moxibustion enhances learning and memory in mice with Alzheimer's disease by reducing amyloid-beta and tau proteins. This improvement is linked to decreased N6-methyladenosine (m6A) levels.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Alzheimer's disease is characterized by amyloid-beta (Aβ) and tau protein pathology.
- N6-methyladenosine (m6A) RNA modification is implicated in neurodegenerative diseases.
- Investigating novel therapeutic interventions for Alzheimer's is crucial.
Purpose of the Study:
- To determine if moxibustion can improve learning and memory in APP/PS1 mice.
- To investigate if moxibustion reduces Aβ and tau pathology by modulating m6A levels.
- To explore the role of m6A and its binding enzyme YTHDF1 in moxibustion's effects.
Main Methods:
- APP/PS1 mice were treated with moxibustion and compared to control groups.
- Morris water maze was used to assess cognitive function.
- Immunofluorescence, Western blot, and q-PCR were employed to measure protein and RNA levels, including Aβ, tau, p-tau, YTHDF1, METTL3, FTO, and m6A.
Main Results:
- Moxibustion significantly improved spatial learning and memory in APP/PS1 mice.
- Treatment reduced levels of Aβ, tau, and p-tau proteins in the hippocampus and cortex.
- Moxibustion decreased overall m6A levels and altered YTHDF1 expression in the brain.
Conclusions:
- Moxibustion demonstrates therapeutic potential for improving cognitive deficits in Alzheimer's models.
- The beneficial effects are associated with reduced Aβ and tau pathology.
- Modulation of m6A RNA methylation and YTHDF1 expression may underlie moxibustion's neuroprotective mechanisms.
