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[Moxibustion improves learning-memory ability by promoting cellular autophagy and regulating autophagy-related proteins in hippocampus and cerebral cortex in APP/PS1 transgenic Alzheimer's disease mice].
Zhen Ci Yan Jiu. 2019 Apr 25; 44(4):235-41.ZC

Abstract

OBJECTIVE

To observe the effect of moxibustion of acupoints of the Governor Vessel on the levels of cellular autophagy, β amyloid protein (Aβ) immunoactivity, and expression of LC3-Ⅰ, LC3-Ⅱ, p62 and p-P70S6K proteins in the hippocampal tissue of APPswe/PS1de9 (APP/PS1) double-transgenic Alzheimer's disease (AD) mice, so as to reveal its underlying mechanisms in improving AD.

METHODS

APP/PS1 double-transgenic AD mice were randomly divided into AD model, moxibustion, autophagy-inducer (Rapamycin) and autophagy-inhibitor (3-MA)+moxibustion groups (n=10 in each group), and other 10 C57BL/6J male mice (the same age) were used as the normal control group. Herbal-cake (made of Chuanwu [Radix Aconiti Praeparata]) partitioned moxibustion was applied to "Baihui"(GV20), moxibustion was applied to "Fengfu"(GV16) and "Dazhui"(GV14), all for 20 min, once daily for 2 weeks, with one day's off between two weeks. For mice of the autophagy-inducer and 3-MA+moxibustion groups, Rapamycin (2 mg•kg-1•d-1) and 3-MA (1.5 mg•kg-1•d-1) were separately administered by intraperitoneal injection for 2 weeks. The cognitive ability was examined by Morris water maze tests, and the ultrastructural changes (including autophagic lysosomes, etc.) of hippocampal neurons were observed by using transmission electron microscopy. The immunoactivity of cerebral cortex and hippocampal Amyloid β peptide 1-42 (Aβ1-42) was detected by immunohistochemistry, and the expression levels of hippocampal LC3-Ⅰ, LC3-Ⅱ, p62 and p-P70S6K proteins were detected by Western blot.

RESULTS

After modeling, the escape latency of Morris water maze tasks was prolonged in the model group than in the normal control group (P<0.05) and obviously shortened in the moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.05). Results of transmission electron microscope showed deformed, irregular or atrophic neurons with rough and incomplete and fuzzy nuclear membrane, and decreased intracellular autophagosomes in the hippocampus in the model group, and partial irregular, atrophic neurons with more autophagic vesicles and lysosomes in the moxibustion group. The expression levels of Aβ1-42 in both cerebral cortex and hippocampus tissues, and LC3-Ⅰ, p62 and p-P70S6K proteins in the hippocampus were consi-derably up-regulated in the model group relevant to the normal control group (P<0.01), and evidently down-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01), while that of hippocampal LC3-Ⅱ protein and LC3-Ⅱ/Ⅰ ratio levels were obviously down-regulated in the model group relevant to the normal control group (P<0.01), and significantly up-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01)..

CONCLUSION

Moxibustion can improve the cognitive ability of APP/PS1 double-transgenic AD mice, which is associated with its effects in promoting hip-pocampal and cerebral cortex autophagy level, and down-regulating the expression levels of Aβ1-42, LC3-Ⅰ, p62 and p-P70S6K proteins in the hippocampus.

Authors+Show Affiliations

Department of Geriatrics, the Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061, China.School of Graduates, Anhui University of Chinese Medicine, Hefei 230038.Institute of Acupuncture and Meridian, Anhui University of Chinese Medicine, Hefei 230038.Department of Acupuncture-moxibustion and Rehabilitation, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230038.Department of Geriatrics, the Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061, China.Department of Geriatrics, the Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061, China.Department of Geriatrics, the Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061, China.Department of Geriatrics, the Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061, China.School of Graduates, Anhui University of Chinese Medicine, Hefei 230038.

Pub Type(s)

Journal Article

Language

chi

PubMed ID

31056874

Citation

Zhu, Cai-Feng, et al. "[Moxibustion Improves Learning-memory Ability By Promoting Cellular Autophagy and Regulating Autophagy-related Proteins in Hippocampus and Cerebral Cortex in APP/PS1 Transgenic Alzheimer's Disease Mice]." Zhen Ci Yan Jiu = Acupuncture Research, vol. 44, no. 4, 2019, pp. 235-41.
Zhu CF, Zhang LD, Song XG, et al. [Moxibustion improves learning-memory ability by promoting cellular autophagy and regulating autophagy-related proteins in hippocampus and cerebral cortex in APP/PS1 transgenic Alzheimer's disease mice]. Zhen Ci Yan Jiu. 2019;44(4):235-41.
Zhu, C. F., Zhang, L. D., Song, X. G., Yang, J., Pan, H. P., He, C. G., Yang, K., Qin, X. F., & Zhu, W. L. (2019). [Moxibustion improves learning-memory ability by promoting cellular autophagy and regulating autophagy-related proteins in hippocampus and cerebral cortex in APP/PS1 transgenic Alzheimer's disease mice]. Zhen Ci Yan Jiu = Acupuncture Research, 44(4), 235-41. https://doi.org/10.13702/j.1000-0607.180305
Zhu CF, et al. [Moxibustion Improves Learning-memory Ability By Promoting Cellular Autophagy and Regulating Autophagy-related Proteins in Hippocampus and Cerebral Cortex in APP/PS1 Transgenic Alzheimer's Disease Mice]. Zhen Ci Yan Jiu. 2019 Apr 25;44(4):235-41. PubMed PMID: 31056874.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Moxibustion improves learning-memory ability by promoting cellular autophagy and regulating autophagy-related proteins in hippocampus and cerebral cortex in APP/PS1 transgenic Alzheimer's disease mice]. AU - Zhu,Cai-Feng, AU - Zhang,Li-da, AU - Song,Xiao-Ge, AU - Yang,Jun, AU - Pan,Hong-Ping, AU - He,Cheng-Gong, AU - Yang,Kun, AU - Qin,Xiao-Feng, AU - Zhu,Wan-Li, PY - 2019/5/7/entrez PY - 2019/5/6/pubmed PY - 2019/5/10/medline KW - APP/PS1 double-transgenic Alzheimer’s disease mice KW - Autophagy KW - Aβ1-42 protein KW - Herbal cake-partitioned moxibustion KW - Learning-memory ability SP - 235 EP - 41 JF - Zhen ci yan jiu = Acupuncture research JO - Zhen Ci Yan Jiu VL - 44 IS - 4 N2 - OBJECTIVE: To observe the effect of moxibustion of acupoints of the Governor Vessel on the levels of cellular autophagy, β amyloid protein (Aβ) immunoactivity, and expression of LC3-Ⅰ, LC3-Ⅱ, p62 and p-P70S6K proteins in the hippocampal tissue of APPswe/PS1de9 (APP/PS1) double-transgenic Alzheimer's disease (AD) mice, so as to reveal its underlying mechanisms in improving AD. METHODS: APP/PS1 double-transgenic AD mice were randomly divided into AD model, moxibustion, autophagy-inducer (Rapamycin) and autophagy-inhibitor (3-MA)+moxibustion groups (n=10 in each group), and other 10 C57BL/6J male mice (the same age) were used as the normal control group. Herbal-cake (made of Chuanwu [Radix Aconiti Praeparata]) partitioned moxibustion was applied to "Baihui"(GV20), moxibustion was applied to "Fengfu"(GV16) and "Dazhui"(GV14), all for 20 min, once daily for 2 weeks, with one day's off between two weeks. For mice of the autophagy-inducer and 3-MA+moxibustion groups, Rapamycin (2 mg•kg-1•d-1) and 3-MA (1.5 mg•kg-1•d-1) were separately administered by intraperitoneal injection for 2 weeks. The cognitive ability was examined by Morris water maze tests, and the ultrastructural changes (including autophagic lysosomes, etc.) of hippocampal neurons were observed by using transmission electron microscopy. The immunoactivity of cerebral cortex and hippocampal Amyloid β peptide 1-42 (Aβ1-42) was detected by immunohistochemistry, and the expression levels of hippocampal LC3-Ⅰ, LC3-Ⅱ, p62 and p-P70S6K proteins were detected by Western blot. RESULTS: After modeling, the escape latency of Morris water maze tasks was prolonged in the model group than in the normal control group (P<0.05) and obviously shortened in the moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.05). Results of transmission electron microscope showed deformed, irregular or atrophic neurons with rough and incomplete and fuzzy nuclear membrane, and decreased intracellular autophagosomes in the hippocampus in the model group, and partial irregular, atrophic neurons with more autophagic vesicles and lysosomes in the moxibustion group. The expression levels of Aβ1-42 in both cerebral cortex and hippocampus tissues, and LC3-Ⅰ, p62 and p-P70S6K proteins in the hippocampus were consi-derably up-regulated in the model group relevant to the normal control group (P<0.01), and evidently down-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01), while that of hippocampal LC3-Ⅱ protein and LC3-Ⅱ/Ⅰ ratio levels were obviously down-regulated in the model group relevant to the normal control group (P<0.01), and significantly up-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01).. CONCLUSION: Moxibustion can improve the cognitive ability of APP/PS1 double-transgenic AD mice, which is associated with its effects in promoting hip-pocampal and cerebral cortex autophagy level, and down-regulating the expression levels of Aβ1-42, LC3-Ⅰ, p62 and p-P70S6K proteins in the hippocampus. SN - 1000-0607 UR - https://www.unboundmedicine.com/medline/citation/31056874/[Moxibustion_improves_learning_memory_ability_by_promoting_cellular_autophagy_and_regulating_autophagy_related_proteins_in_hippocampus_and_cerebral_cortex_in_APP/PS1_transgenic_Alzheimer's_disease_mice]_ L2 - https://medlineplus.gov/alzheimersdisease.html DB - PRIME DP - Unbound Medicine ER -