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- Hai-Dong Guo, Jing Zhu, Jin-Xin Tian, Shui-Jin Shao, Yan-Wu Xu, Fang-Fang Mou, Xiao-Jing Han, Zhi-Hua Yu, Jiu-Lin Chen, Da-Yong Zhang, Li-Sheng Zhang, and Guo-Hong Cui.
- Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
- Acupunct Med. 2016 Dec 1; 34 (6): 449-456.
BackgroundAcupuncture 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.MethodsWe injected 2μl Aβ1-40 bilaterally 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 Aβ1-40 was examined.ResultsIn 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.ConclusionsEA reduces neuronal apoptosis, enhances degradation of Aβ, and improves learning/memory in AD rats by upregulating the autophagy pathway.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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