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[Effect of electroacupuncture combined with Donepezil on learning-memory ability and expression of hippocampal β-amyloid clearance-related genes in SAMP8 mice].
Zhen Ci Yan Jiu. 2020 Apr 25; 45(4):281-6.ZC

Abstract

OBJECTIVE

To investigate the effect of electroacupuncture (EA) combined with Donepezil on learning-memory ability and gene expression of β-amyloid (Aβ) clearance-related factors in the hippocampus in senescence-accelerated mouse prone 8 (SAMP8) mice, so as to explore their synthetic effect in improving dementia of Alzheimer's disease (AD)..

METHODS

Male SAMP8 mice (30-week-old) were randomly divided into model, medication and EA+medication groups (n=6 mice in each group), and other 6 senescence-resistant 1 (SAMR1) mice were used as the control group. Mice of the medication and EA+medication group received gavage of Donepezil (1.3 mg•kg-1•d-1) once daily for 4 weeks. EA (2 Hz, 1 mA) was applied to "Baihui"(GV20) and "Yintang" (EX-HN3) for 15 min, once daily, 6 days a week for 4 weeks for rats in the EA+medication group. The Morris water maze (MWM) task (including place navigation tests and space exploration trials) was used to assess the mouse's learning-memory ability. Histopathological changes of hippocampus tissue were observed by H.E. staining. The expression levels of matrix metalloprotein 9 (MMP-9), low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (Pgp, an important drug transporter responsible for multidrug resistance), Claudin-5 (a component of tight junction strands that serves as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets of blood-brain barrier, BBB) and Aβ mRNAs of the hippocampus tissue were detected by quantitative real-time PCR.

RESULTS

Compared with the control group, the average escape latency of place navigation tests, and the expression levels of MMP-9 and Aβ mRNAs were significantly increased (P<0.01), and the number of platform quadrant-crossing times of space exploration trials, and the expression levels of LRP-1, Pgp and Claudin-5 mRNAs considerably decreased in the model group (P<0.01). After the intervention, the learning-memory ability was significantly improved in the medication and EA+medication groups (P<0.01,P<0.05), the expression levels of Aβ mRNAs in the medication and EA+medication groups and MMP-9 mRNA in the EA+medication group were obviously down-regulated (P<0.01), and those of LRP-1 and Pgp mRNAs in the medication and EA+medication groups and Claudin-5 mRNA in the EA+medication group were remarkably up-regulated (P<0.05, P<0.01). The therapeutic effect of EA+medication was apparently superior to that of simple medication in shortening the escape latency (P<0.05,P<0.01) and in down-regulating the expression of MMP-9 and Aβ mRNAs(P<0.01), and in increasing the number of platform quadrant-crossing times(P<0.01), and expression levels of LRP-1, Pgp and Claudin-5 mRNAs (P<0.01). H.E. staining showed scatted and loose arrangement of neurons in the hippocampus, with reduction of number of cell layers and unclear nucleoli, which was relatively milder in the medication and EA+medication groups.

CONCLUSION

EA can enhance the effect of Donepezil in improving learning-memory ability in AD mice possibly by regulating expression of MMP-9, LRP-1, Pgp and Claudin-5 mRNAs and strengthening the effect of Donepezil in transporting Aβ via BBB.

Authors+Show Affiliations

College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.Department of Rehabilitation, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016.College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.

Pub Type(s)

Journal Article

Language

chi

PubMed ID

32333532

Citation

Yang, Zhi-Xue, et al. "[Effect of Electroacupuncture Combined With Donepezil On Learning-memory Ability and Expression of Hippocampal Β-amyloid Clearance-related Genes in SAMP8 Mice]." Zhen Ci Yan Jiu = Acupuncture Research, vol. 45, no. 4, 2020, pp. 281-6.
Yang ZX, Tang CL, Li XH, et al. [Effect of electroacupuncture combined with Donepezil on learning-memory ability and expression of hippocampal β-amyloid clearance-related genes in SAMP8 mice]. Zhen Ci Yan Jiu. 2020;45(4):281-6.
Yang, Z. X., Tang, C. L., Li, X. H., Zhu, Z. W., Qiu, L., An, H. Y., Wu, M. J., & Yang, Y. H. (2020). [Effect of electroacupuncture combined with Donepezil on learning-memory ability and expression of hippocampal β-amyloid clearance-related genes in SAMP8 mice]. Zhen Ci Yan Jiu = Acupuncture Research, 45(4), 281-6. https://doi.org/10.13702/j.1000-0607.190081
Yang ZX, et al. [Effect of Electroacupuncture Combined With Donepezil On Learning-memory Ability and Expression of Hippocampal Β-amyloid Clearance-related Genes in SAMP8 Mice]. Zhen Ci Yan Jiu. 2020 Apr 25;45(4):281-6. PubMed PMID: 32333532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effect of electroacupuncture combined with Donepezil on learning-memory ability and expression of hippocampal β-amyloid clearance-related genes in SAMP8 mice]. AU - Yang,Zhi-Xue, AU - Tang,Cheng-Lin, AU - Li,Xiao-Hong, AU - Zhu,Zheng-Wei, AU - Qiu,Li, AU - An,Hui-Yu, AU - Wu,Meng-Jia, AU - Yang,Yun-Hao, PY - 2020/4/26/entrez PY - 2020/4/26/pubmed PY - 2020/6/26/medline KW - Alzheimer’s disease KW - Blood-brain barrier KW - Donepezil KW - Electroacupuncture KW - Learning-memory ability KW - β-amyloid SP - 281 EP - 6 JF - Zhen ci yan jiu = Acupuncture research JO - Zhen Ci Yan Jiu VL - 45 IS - 4 N2 - OBJECTIVE: To investigate the effect of electroacupuncture (EA) combined with Donepezil on learning-memory ability and gene expression of β-amyloid (Aβ) clearance-related factors in the hippocampus in senescence-accelerated mouse prone 8 (SAMP8) mice, so as to explore their synthetic effect in improving dementia of Alzheimer's disease (AD).. METHODS: Male SAMP8 mice (30-week-old) were randomly divided into model, medication and EA+medication groups (n=6 mice in each group), and other 6 senescence-resistant 1 (SAMR1) mice were used as the control group. Mice of the medication and EA+medication group received gavage of Donepezil (1.3 mg•kg-1•d-1) once daily for 4 weeks. EA (2 Hz, 1 mA) was applied to "Baihui"(GV20) and "Yintang" (EX-HN3) for 15 min, once daily, 6 days a week for 4 weeks for rats in the EA+medication group. The Morris water maze (MWM) task (including place navigation tests and space exploration trials) was used to assess the mouse's learning-memory ability. Histopathological changes of hippocampus tissue were observed by H.E. staining. The expression levels of matrix metalloprotein 9 (MMP-9), low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (Pgp, an important drug transporter responsible for multidrug resistance), Claudin-5 (a component of tight junction strands that serves as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets of blood-brain barrier, BBB) and Aβ mRNAs of the hippocampus tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the average escape latency of place navigation tests, and the expression levels of MMP-9 and Aβ mRNAs were significantly increased (P<0.01), and the number of platform quadrant-crossing times of space exploration trials, and the expression levels of LRP-1, Pgp and Claudin-5 mRNAs considerably decreased in the model group (P<0.01). After the intervention, the learning-memory ability was significantly improved in the medication and EA+medication groups (P<0.01,P<0.05), the expression levels of Aβ mRNAs in the medication and EA+medication groups and MMP-9 mRNA in the EA+medication group were obviously down-regulated (P<0.01), and those of LRP-1 and Pgp mRNAs in the medication and EA+medication groups and Claudin-5 mRNA in the EA+medication group were remarkably up-regulated (P<0.05, P<0.01). The therapeutic effect of EA+medication was apparently superior to that of simple medication in shortening the escape latency (P<0.05,P<0.01) and in down-regulating the expression of MMP-9 and Aβ mRNAs(P<0.01), and in increasing the number of platform quadrant-crossing times(P<0.01), and expression levels of LRP-1, Pgp and Claudin-5 mRNAs (P<0.01). H.E. staining showed scatted and loose arrangement of neurons in the hippocampus, with reduction of number of cell layers and unclear nucleoli, which was relatively milder in the medication and EA+medication groups. CONCLUSION: EA can enhance the effect of Donepezil in improving learning-memory ability in AD mice possibly by regulating expression of MMP-9, LRP-1, Pgp and Claudin-5 mRNAs and strengthening the effect of Donepezil in transporting Aβ via BBB. SN - 1000-0607 UR - https://www.unboundmedicine.com/medline/citation/32333532/[Effect_of_electroacupuncture_combined_with_Donepezil_on_learning_memory_ability_and_expression_of_hippocampal_β_amyloid_clearance_related_genes_in_SAMP8_mice]_ L2 - https://antibodies.cancer.gov/detail/CPTC-OTUB1-1 DB - PRIME DP - Unbound Medicine ER -