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      Effect of the electro-acupuncture on senile plaques and its formation in APP +/PS1 + double transgenic mice

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          Abstract

          Alzheimer's disease (AD) is a progressive neurodegenerative disease and its incidence will increase with age and is aggravating. The senile plaques (SPs) are one of three main pathological features in AD patients, which are formed by amyloid β-protein (Aβ) over-accumulation. β-amyloid precursor protein (APP), β-site APP cleavage (BACE1), and insulin degrading enzyme (IDE) proteins participate in the process of Aβ production and degradation. At present, the pathogenesis of AD is not yet clear and the current treatment methods can only relief the related symptoms of AD. The electro-acupuncture (EA) is a traditional Chinese medicine treatment combined the acupuncture and electrical stimulation and the treatment effect can also be controlled by transform the electrical frequency. Thus, in this experiment, we carried out behavioral test, immunohistochemistry (IHC), and Western Blot (WB) after different period treatments to the model mice by electro-acupuncturing “Baihui” and “Shenshu” acupoints in APP +/PS1 + double transgenic mice. It was found that the EA therapy can improve the ability of learning, memory and spatial exploration, and reduce the deposition of SPs in brain of AD model mice, and reduce the expressions of APP and BACE1, increase the expression of IDE protein. These results prompt that EA can effectively alleviate the pathological process of AD. We speculate that EA may play a comprehensive role in preventing the development of AD, considering the previous data.

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          Acupuncture stimulation improves scopolamine-induced cognitive impairment via activation of cholinergic system and regulation of BDNF and CREB expressions in rats

          Background Acupuncture is an alternative therapy that is widely used to treat various neurodegenerative diseases and effectively improve cognitive and memory impairment. The aim of this study was to examine whether acupuncture stimulation at the Baihui (GV20) acupoint improves memory defects caused by scopolamine (SCO) administration in rats. We also investigated the effects of acupuncture stimulation at GV20 on the cholinergic system as well as the expression of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) in the hippocampus. Methods SCO (2 mg/kg, i.p.) was administered to male rats once daily for 14 days. Acupuncture stimulation at GV20 was performed for 5 min before SCO injection. After inducing cognitive impairment via SCO administration, we conducted a passive avoidance test (PAT) and the Morris water maze (MWM) test to assess behavior. Results Acupuncture stimulation at GV20 improved memory impairment as measured by the PAT and reduced the escape latency for finding the platform in the MWM test. Acupuncture stimulation at GV20 significantly alleviated memory-associated decreases in the levels of choline acetyltransferase (ChAT), BDNF and CREB proteins in the hippocampus. Additionally, acupuncture stimulation at GV20 significantly restored the expression of choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), BDNF and CREB mRNA in the hippocampus. These results demonstrate that acupuncture stimulation at GV20 exerts significant neuroprotective effects against SCO-induced neuronal impairment and memory dysfunction in rats. Conclusions These findings suggest that acupuncture stimulation at GV20 might be useful in various neurodegenerative diseases to improve cognitive functioning via stimulating cholinergic enzyme activities and regulating BDNF and CREB expression in the brain.
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            Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture.

            An essential feature of Alzheimer's disease (AD) is implicated in brain energy metabolic impairment that is considered underlying pathogenesis of cognitive impairment. Therefore, therapeutic interventions to allay cognitive deficits that target energy metabolism may be an efficacy strategy in AD. In this study, we found that electroacupuncture (EA) at the DU20 acupoint obviously increased glucose metabolism in specific brain regions such as cortex, hippocampus, cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1 transgenic mice by animal 18F-Fluoro-2-deoxy-D-Glucose (18F-FDG)/positron emission tomography (PET) imaging, accompanied by cognitive improvements in the spatial reference learning and memory and memory flexibility and novel object recognition performances. Further evidence shown energy metabolism occurred in neurons or non-neuronal cells of the cortex and hippocampus in terms of the co-location of GLUT3/NeuN and GLUT1/GFAP. Simultaneously, metabolic homeostatic factors were critical for glucose metabolism, including phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and AKT serine/threonine kinase. Furthermore, EA-induced phosphorylated AMPK and AKT inhibited the phosphorylation level of the mammalian target of rapamycin (mTOR) to decrease the accumulation of amyloid-beta (Aβ) in the cortex and hippocampus. These findings are concluded that EA is a potential therapeutic target for delaying memory decline and Aβ deposition of AD. The AMPK and AKT are implicated in the EA-induced cortical and hippocampal energy metabolism, which served as a contributor to improving cognitive function and Aβ deposition in a transgenic mouse model of AD.
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              Acupuncture improves cognitive deficits and regulates the brain cell proliferation of SAMP8 mice.

              Senescence-accelerated mouse prone 8 (SAMP8) is an autogenic senile strain characterized by early cognitive impairment and age-related deterioration of learning and memory. To investigate the effect of acupuncture on behavioral changes and brain cell events, male 4-month-old SAMP8 and age-matched homologous normal aging SAMR1 mice were divided into four groups: SAMP8 acupuncture group (Pa), SAMP8 non-acupoint control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). By Morris water maze test, the cognitive deficit of SAMP8 was revealed and significantly improved by "Yiqitiaoxue and Fubenpeiyuan" acupuncture. Meanwhile, by 5'-bromo-2'-deoxyuridine (BrdU) specific immunodetection, the decreased cell proliferation in dentate gyrus (DG) of SAMP8 was greatly enhanced by the therapeutic acupuncture, suggesting acupoint-related specificity. Even though no significant differences were found in ventricular/subventricular zones (VZ/SVZ) of the third ventricle (V3) and lateral ventricle (LV) between groups, we obtained interesting results: a stream-like distribution of newly proliferated cells presented along the dorsum of alveus hippocampi (Alv), extending from LV to corpus callosum (CC), and the therapeutic acupuncture showed a marked effect on this region. Our research suggests that acupuncture can induce different cell proliferation in different brain regions of SAMP8, which brings forth the need to explore further for the mechanism of cognitive deficits and acupuncture intervention in this field.
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                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-4820
                2352-3042
                15 June 2018
                September 2019
                15 June 2018
                : 6
                : 3
                : 282-289
                Affiliations
                [a ]Institute of Neuroscience, Chongqing Medical University, Chongqing, China
                [b ]College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China
                Author notes
                [] Corresponding author. Department of Human Anatomy, Chongqing Medical University, 1st on Yixueyuan Road, Yuzhong District, Chongqing, 400016, China. Fax: +86 23 68485868. shjxxh@ 123456sina.com
                [1]

                These authors contributed equally to this work.

                Article
                S2352-3042(18)30066-7
                10.1016/j.gendis.2018.06.002
                6997572
                32042867
                ab3acd32-60be-4fae-a67f-d75a20067aa4
                © 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 1 May 2018
                : 5 June 2018
                Categories
                Article

                alzheimer's disease,amyloid β-protein,electro-acupuncture,senile plaques,transgenic mice,ad, alzheimer's disease,aβ, amyloid β-protein,sps, senile plaques,app, β-,amyloid precursor protein, bace1,β-, site app cleavage,ide, insulin degrading enzyme,ea, electro-acupuncture,ihc, immunohistochemistry,sod, superoxide dismutase,ach, aetylcholine,chat, aetylcholine tansferase,ache, cholinesterase

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