title: Electroacupuncture improves memory and protects neurons by regulation of the autophagy pathway in a rat model of Alzheimer's disease.
abstract: BACKGROUND
  Acupuncture is a potential therapy for Alzheimer's disease (AD), but its clinical effects and underlying mechanisms are not fully understood. Emerging evidence suggests autophagy is involved in β-amyloid (Aβ) clearance. We hypothesised that electroacupuncture (EA) treatment of AD involves the autophagy pathway in rats.
  
  
  METHODS
  We injected 2μl Aβ1-40bilaterally into the hippocampi of 42 rats to establish AD. Rats remained untreated (AD group, n=14) or received 24 EA treatments at GV20+BL23 over 28 days from day 7 post-injection with/without co-treatment with 3-methyladenine (3-MA), an autophagy inhibitor (AD+EA+3-MA and AD+EA groups, respectively, n=14 each). Cognitive function was evaluated by Morris water maze (MWM) testing. Hippocampi were examined by transmission electron microscopy (TEM) and stained with haematoxylin and eosin/transferase dUTP nick end labelling (TUNEL) to assess neuronal morphology/apoptosis, respectively. Protein expression of Beclin-1, LC3 and Aβ1-40was examined.
  
  
  RESULTS
  In the MWM test, the AD+EA group showed an improvement in parameters consistent with improved learning/memory compared to untreated AD rats, and 3-MA attenuated these effects. EA mitigated cellular apoptosis resulting from Aβ infusion in the CA1 region and enhanced LC3II/LC3I ratios and Beclin-1 expression. Numerous autophagosome precursors and enlarged autophagosomes were observed by TEM in the hippocampi of EA-treated rats. Reduced Aβ levels, and co-localisation of Aβ and LC3II, were observed following EA treatment by immunofluorescence staining. EA+3-MA treated rats had much higher TUNEL-positive neurons, lower LC3II/LC3I ratios and Beclin-1 expression, and elevated Aβ levels compared with EA alone.
  
  
  CONCLUSIONS
  EA reduces neuronal apoptosis, enhances degradation of Aβ, and improves learning/memory in AD rats by upregulating the autophagy pathway.
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Guo
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Tian
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Shui-Jin
authors.initials: SJ
authors.lastname: Shao
authors.affiliation: Department of Biochemistry, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yan-Wu
authors.initials: YW
authors.lastname: Xu
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Mou
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Han
authors.affiliation: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Yu
authors.affiliation: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jiu-Lin
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Zhejiang University City College, Hangzhou, Zhejiang, China.
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Cui
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1 / Q000378:metabolism; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D006624:Hippocampus / Q000503:physiopathology; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000628:therapy*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats
chemical_list: D000225:Adenine; D016229:Amyloid beta-Peptides; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C078592:amyloid beta-protein (1-40); C025946:3-methyladenine