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[Moxibustion at acpoints of governor vessel on regulating PI3K/Akt/mTOR signaling pathway and enhancing autophagy process in APP/PS1 double-transgenic Alzheimer's disease mice].
Zhongguo Zhen Jiu. 2019 Dec 12; 39(12):1313-8.ZZ

Abstract

OBJECTIVE

To observe the eliminating effects of moxibustion at "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) on amyloid β-peptide (Aβ) in brain of the amyloid precursor protein/presenili1 (APP/PS1) double-transgenic mice with Alzheimer's disease (AD) by regulating the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway.

METHODS

A total of 60 APP/PS1 double-transgenic mice with AD were randomly divided into a model group, a moxibustion group, a rapamycin group and a combination group (treated with moxibustion and inhibitor), 15 mice in each group, another 15 male C57BL/6J mice with same age and background were selected as the control group. In the moxibustion group, pressing moxibustion was applied at "Baihui" (GV 20) while the mild moxibustion was applied at "Fengfu" (GV 16) and "Dazhui" (GV 14). The treatment was manipulated for 20 min each time, once a day for 2 weeks. In the rapamycin group, rapamycin (2 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. On the basis of the treatment in the moxibustion group, 3-methyladenine (1.5 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. The mice in the control and the model group received normal diet and no intervention was given for 2 weeks. Immunohistochemica method was used to measure the levels of Aβ1-42 in the cerebral cortex and hippocampal, transmission electron microscopy was used to observe the formation of autophagosome in hippocampus, and Western blot method was used to observe the levels of PI3K, Akt, p-Akt, mTOR and p-mTOR in hippocampus.

RESULTS

Compared with the control group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were increased in the model group (P<0.01). Compared with the model group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were decreased in the moxibustion group, the rapamycin group and the combination group (all P<0.01), compared with the moxibustion group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were increased in the combination group (P<0.01), while there was no significant difference between the moxibustion group and the rapamycin group in the levels of Aβ1-42(P>0.05). Compared with the rapamycin group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were increased in the combination group (P<0.01). In the model group, the cytoplasmic utophagic vacuoles and organelles of neuron were reduced. In the moxibustion group, the utophagic vacuoles were increased, and the organelles showed deformation and atrophy. In the rapamycin group, the utophagic vacuoles were widely disturbed and few deformed organelles were found. In the combination group, few utophagic vacuoles were found and additional organelles showed deformation and atrophy. Compared with the control group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the model group (all P<0.01). Compared with the model group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were reduced in the moxibustion group, the rapamycin group and the combination group (all P<0.01). Compared with the moxibustion group, the levels of PI3K、Akt、and p-mTOR were increased in the rapamycin group and the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (all P<0.01). Compared with the rapamycin group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (P<0.01).

CONCLUSION

Moxibustion at acupoints of governor vessel can enhance the autophagy process on Aβ1-42 in brain of the APP/PS1 double-transgenic AD mice, which may be associated with its effects on inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway.

Authors+Show Affiliations

Graduate School of Anhui University of CM, Hefei 230038, China.Department of Encephalopathy, 3Department of Geriatrics, Second Affiliated Hospital of Anhui University of CM, Hefei 230061.Department of Geriatrics, Second Affiliated Hospital of Anhui University of CM, Hefei 230061.Institute of Acupuncture and Meridian, Anhui University of CM.Experimental Research Center, Anhui University of CM, Key Laboratory of Xin'an Medicine, Ministry of Education.Department of Geriatrics, Second Affiliated Hospital of Anhui University of CM, Hefei 230061.Department of Geriatrics, Second Affiliated Hospital of Anhui University of CM, Hefei 230061.Department of Geriatrics, Second Affiliated Hospital of Anhui University of CM, Hefei 230061.Graduate School of Anhui University of CM, Hefei 230038, China.

Pub Type(s)

Journal Article

Language

chi

PubMed ID

31820607

Citation

Zhang, Li-da, et al. "[Moxibustion at Acpoints of Governor Vessel On Regulating PI3K/Akt/mTOR Signaling Pathway and Enhancing Autophagy Process in APP/PS1 Double-transgenic Alzheimer's Disease Mice]." Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion, vol. 39, no. 12, 2019, pp. 1313-8.
Zhang LD, Han W, Zhu CF, et al. [Moxibustion at acpoints of governor vessel on regulating PI3K/Akt/mTOR signaling pathway and enhancing autophagy process in APP/PS1 double-transgenic Alzheimer's disease mice]. Zhongguo Zhen Jiu. 2019;39(12):1313-8.
Zhang, L. D., Han, W., Zhu, C. F., Song, X. G., Cheng, H., Yang, K., Qin, X. F., Zhang, J. Y., & Gui, L. (2019). [Moxibustion at acpoints of governor vessel on regulating PI3K/Akt/mTOR signaling pathway and enhancing autophagy process in APP/PS1 double-transgenic Alzheimer's disease mice]. Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion, 39(12), 1313-8. https://doi.org/10.13703/j.0255-2930.2019.12.015
Zhang LD, et al. [Moxibustion at Acpoints of Governor Vessel On Regulating PI3K/Akt/mTOR Signaling Pathway and Enhancing Autophagy Process in APP/PS1 Double-transgenic Alzheimer's Disease Mice]. Zhongguo Zhen Jiu. 2019 Dec 12;39(12):1313-8. PubMed PMID: 31820607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Moxibustion at acpoints of governor vessel on regulating PI3K/Akt/mTOR signaling pathway and enhancing autophagy process in APP/PS1 double-transgenic Alzheimer's disease mice]. AU - Zhang,Li-da, AU - Han,Wei, AU - Zhu,Cai-Feng, AU - Song,Xiao-Ge, AU - Cheng,Hui, AU - Yang,Kun, AU - Qin,Xiao-Feng, AU - Zhang,Jun-Yu, AU - Gui,Lin, PY - 2019/12/11/entrez PY - 2019/12/11/pubmed PY - 2020/1/11/medline KW - Alzheimer’s disease KW - PI3K/Akt/mTOR signaling pathway KW - amyloid β-peptide (Aβ) KW - autophagy KW - governor vessel KW - moxibustion SP - 1313 EP - 8 JF - Zhongguo zhen jiu = Chinese acupuncture & moxibustion JO - Zhongguo Zhen Jiu VL - 39 IS - 12 N2 - OBJECTIVE: To observe the eliminating effects of moxibustion at "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) on amyloid β-peptide (Aβ) in brain of the amyloid precursor protein/presenili1 (APP/PS1) double-transgenic mice with Alzheimer's disease (AD) by regulating the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. METHODS: A total of 60 APP/PS1 double-transgenic mice with AD were randomly divided into a model group, a moxibustion group, a rapamycin group and a combination group (treated with moxibustion and inhibitor), 15 mice in each group, another 15 male C57BL/6J mice with same age and background were selected as the control group. In the moxibustion group, pressing moxibustion was applied at "Baihui" (GV 20) while the mild moxibustion was applied at "Fengfu" (GV 16) and "Dazhui" (GV 14). The treatment was manipulated for 20 min each time, once a day for 2 weeks. In the rapamycin group, rapamycin (2 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. On the basis of the treatment in the moxibustion group, 3-methyladenine (1.5 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. The mice in the control and the model group received normal diet and no intervention was given for 2 weeks. Immunohistochemica method was used to measure the levels of Aβ1-42 in the cerebral cortex and hippocampal, transmission electron microscopy was used to observe the formation of autophagosome in hippocampus, and Western blot method was used to observe the levels of PI3K, Akt, p-Akt, mTOR and p-mTOR in hippocampus. RESULTS: Compared with the control group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were increased in the model group (P<0.01). Compared with the model group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were decreased in the moxibustion group, the rapamycin group and the combination group (all P<0.01), compared with the moxibustion group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were increased in the combination group (P<0.01), while there was no significant difference between the moxibustion group and the rapamycin group in the levels of Aβ1-42(P>0.05). Compared with the rapamycin group, the levels of Aβ1-42 in the cerebral cortex and hippocampal were increased in the combination group (P<0.01). In the model group, the cytoplasmic utophagic vacuoles and organelles of neuron were reduced. In the moxibustion group, the utophagic vacuoles were increased, and the organelles showed deformation and atrophy. In the rapamycin group, the utophagic vacuoles were widely disturbed and few deformed organelles were found. In the combination group, few utophagic vacuoles were found and additional organelles showed deformation and atrophy. Compared with the control group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the model group (all P<0.01). Compared with the model group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were reduced in the moxibustion group, the rapamycin group and the combination group (all P<0.01). Compared with the moxibustion group, the levels of PI3K、Akt、and p-mTOR were increased in the rapamycin group and the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (all P<0.01). Compared with the rapamycin group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (P<0.01). CONCLUSION: Moxibustion at acupoints of governor vessel can enhance the autophagy process on Aβ1-42 in brain of the APP/PS1 double-transgenic AD mice, which may be associated with its effects on inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway. SN - 0255-2930 UR - https://www.unboundmedicine.com/medline/citation/31820607/[Moxibustion_at_acpoints_of_governor_vessel_on_regulating_PI3K/Akt/mTOR_signaling_pathway_and_enhancing_autophagy_process_in_APP/PS1_double_transgenic_Alzheimer's_disease_mice]_ L2 - https://medlineplus.gov/alzheimersdisease.html DB - PRIME DP - Unbound Medicine ER -