Alzheimer’s Disease






Zhen Ci Yan Jiu. 2012 Oct;37(5):422-7.
[Progress of researches on mechanisms of acupuncture intervention of Alzheimer's disease].
[Article in Chinese]
Zhu J, Guo HD, Shao SJ.
Source
Teaching and Study Section of Anatomy, Basic Medical College, Shanghai University of Chinese Medicine, Shanghai 201203, China. zhujing0208@163.com
Abstract
Alzheimer's disease (AD) is one of the major diseases threatening the aged people's health. In the present paper, the authors reviewed development of studies on acupuncture treatment of AD from: 1) regulating release of neurotransmitters (cholinergic, amino-acids and monoamine neurotransmitters), 2) protecting cerebral neurons from apoptosis (anti-oxidative stress, improving synaptic plasticity, and suppressing apoptosis), 3) improving levels of neurotrophic factors, 4) regulating hippocampal intracellular signaling, 5) inhibiting inflammatory reactions of the brain tissue, 6) adjusting the level of abnormal proteins (microtubule-associated protein, beta-amyloid), and 7) up-regulating the level of autophagy activity. However, current experimental studies can not completely answer clinical questions due to limited model designs and complicated pathological mechanisms of AD. Many findings of biological indexes need being verified further. Reasonable therapeutic regimens of acupuncture formulated according to syndrome differentiation will help improving clinical curative effect and the corresponding research on new therapeutic targets may be helpful to our understanding about the mechanism of acupuncture.

1) regulating release of neurotransmitters (cholinergic, amino-acids and monoamine neurotransmitters)

2) protecting cerebral neurons from apoptosis (anti-oxidative stress, improving synaptic plasticity, and suppressing apoptosis)

3) improving levels of neurotrophic factors,

4) regulating hippocampal intracellular signaling

5) inhibiting inflammatory reactions of the brain tissue

6) adjusting the level of abnormal proteins (microtubule-associated protein, beta-amyloid)

7) up-regulating the level of autophagy activity.












2
Mol Med Rep. 2013 May;7(5):1516-22. doi: 10.3892/mmr.2013.1392. Epub 2013 Mar 22.
Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.





Acupunct Electrother Res. 2012;37(2-3):89-101.
Acute effects of electro-acupuncture (EA) on hippocampal long term potentiation (LTP) of perforant path-dentate gyrus granule cells synapse related to memory.




Zhongguo Zhen Jiu. 2012 Aug;32(8):726-30.
[Effects of electroacupuncture on the function of respiration chain in hippocampal mitochondria of SAMP8 mice ].




Acupunct Med. 2012 Dec;30(4):339-45. doi: 10.1136/acupmed-2012-010180. Epub 2012 Sep 12.
Acupuncture improves cognitive deficits and increases neuron density of the hippocampus in middle-aged SAMP8 mice.




J Altern Complement Med. 2012 Apr;18(4):387-93. doi: 10.1089/acm.2010.0205.
Capturing amplitude changes of low-frequency fluctuations in functional magnetic resonance imaging signal: a pilot acupuncture study on NeiGuan (PC6).




Magn Reson Imaging. 2012 Jun;30(5):672-82. doi: 10.1016/j.mri.2012.01.003. Epub 2012 Mar 27.
FMRI connectivity analysis of acupuncture effects on the whole brain network in mild cognitive impairment patients.




J Tradit Chin Med. 2011 Sep;31(3):178-81.
Clinical research on comprehensive treatment of senile vascular dementia.




[Effect of electroacupuncture on learning-memory ability, and Abeta and LRP1 immunoactivity in hippocampal sulcus microvessels in APP transgenic mice].




Zhen Ci Yan Jiu. 2011 Apr;36(2):90-4.
[Effect of "Xiusanzhen" on hippocampal muscarinic cholinergic receptor activity in Alzheimer disease rats].




Zhen Ci Yan Jiu. 2011 Feb;36(1):7-11.
[Effect of "Xiusanzhen"on expression of hippocampal Bcl-2 and Bax proteins in Alzheimer disease rats].




Front Med Biol Eng. 2002;11(4):237-47.
A study on the rehabilitation of cognitive function and short-term memory in patients with Alzheimer's disease using transcutaneous electrical nerve stimulation.



PLoS One. 2012;7(8):e42730. doi: 10.1371/journal.pone.0042730. Epub 2012 Aug 20.
Effect of acupuncture in mild cognitive impairment and Alzheimer disease: a functional MRI study.
Wang Z, Nie B, Li D, Zhao Z, Han Y, Song H, Xu J, Shan B, Lu J, Li K.
Source
Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China.






Zhongguo Zhen Jiu. 2010 Dec;30(12):1007-10.
[Effects of electroacupuncture on expression of Abeta positive cells of the hippocampus and SOD activity in rats with streptozocin-Alzheimer's disease].
[Article in Chinese]
Zhang P, Guan SS, Jiang GH.
Source
Heilongjiang University of TCM, Harbin 150040, China.





Zhongguo Zhen Jiu. 2009 Feb;29(2):133-6.
[Effects of electroacupuncture on learning and memory ability and glial cells of the hippocampus in the rat of Alzheimer disease].
[Article in Chinese]
Zhu SX, Sun GJ.
Source
TCM Department, College of Medical Sciences, Jianghan University, Wuhan 430065, Hubei, China.





Acupunct Electrother Res. 2008;33(1-2):9-17.
Effect of acupuncture given at the HT 7, ST 36, ST 40 and KI 3 acupoints on various parts of the brains of Alzheimer' s disease patients.
Zhou Y, Jin J.
Source
Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.




Zhongguo Zhen Jiu. 2008 Jan;28(1):37-40.
[Clinical observation on catgut implantation at acupoint for treatment of Alzheimer's disease].
[Article in Chinese]
Zhou YL, Jia JP.
Source
Xuanwu Hospital of Capital Medical University, Beijing 100053, China.




Zhongguo Zhen Jiu. 2005 Jun;25(6):390-2.
[Clinical observation on acupuncture combined with music for treatment of Alzheimer disease].
[Article in Chinese]
Liu G, Yuan LX.
Source
College of Acupuncture and Massage, Guangzhou University of TCM, Guangdong 510405, China. cnlgtcm@163.com





J Tradit Chin Med. 2013 Feb;33(1):46-50.
Clinical observation on effect of scalp electroacupuncture for mild cognitive impairment.
Zhang H, Zhao L, Yang S, Chen Z, Li Y, Peng X, Yang Y, Zhu M.
Source
Department of Acupuncture and Tuina, Chengdu University of Tranditional Chinese Medicine, Chengdu 610075, China. hzhang0123@foxmail.com




Zhongguo Zhen Jiu. 2012 Sep;32(9):779-84.
[Mild cognitive impairment disease treated with electroacupuncture: a multi-center randomized controlled trial].
[Article in Chinese]
Zhao L, Zhang FW, Zhang H, Zhao Y, Zhou B, Chen WY, Zhu MJ.
Source
Chengdu University of TCM, College of Acupuncture-Moxibustion and Massage, Chengdu 610075, Sichuan Province, China. zhaoling@cdutcm.edu.cn




Evid Based Complement Alternat Med. 2013;2013:127271. doi: 10.1155/2013/127271. Epub 2013 Aug 19.
Multivariate granger causality analysis of acupuncture effects in mild cognitive impairment patients: an FMRI study.




J Acupunct Meridian Stud. 2013 Oct;6(5):247-51. doi: 10.1016/j.jams.2013.07.001. Epub 2013 Jul 17.
Laser acupuncture improves memory impairment in an animal model of Alzheimer's disease.




J Tradit Chin Med. 2013 Aug;33(4):461-7.
Ear therapy and massage therapy in the elderly with dementia: a pilot study.
Rodríguez-Mansilla J, González-López-Arza MV, Varela-Donoso E, Montanero-Fernández J, Jiménez-Palomares M, Garrido-Ardila EM.




Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Dec;33(12):1626-30.
[Treating vascular mild cognitive impairment by acupuncture: a systematic review of randomized controlled trials]




Neurol Sci. 2013 Jul;34(7):1093-7. doi: 10.1007/s10072-012-1209-4. Epub 2012 Oct 9.
Effect of electroacupuncture on the expression of mTOR and eIF4E in hippocampus of rats with vascular dementia.
Zhu Y1, Zeng Y, Wang X, Ye X.
Author information




BMC Complement Altern Med. 2014 May 31;14(1):178. [Epub ahead of print]
Brain areas involved in the acupuncture treatment of AD model rats: a PET study.
Lu Y, Huang Y, Tang C, Shan B, Cui S, Yang J, Chen J, Lin R, Xiao H, Qu S, Lai X.




Zhen Ci Yan Jiu. 2014 Apr;39(2):142-7.
[Effect of electroacupuncture intervention at different time-points of post-modeling on hippocampal monoamine neurotransmitter levels in mice with vascular dementia].
[Article in Chinese]
Zhang HZ, Liang YL, Zhang XJ, Zhang C, Sun YH, Zhang XJ, Xu XK, Jia RG, Wang XG.




Neural Regen Res. 2014 May 1;9(9):968-72. doi: 10.4103/1673-5374.133148.
Acupuncture and moxibustion reduces neuronal edema in Alzheimer's disease rats.
Zhou H, Sun G, Kong L, Du Y, Shen F, Wang S, Chen B, Zeng X.
Author information




Zhen Ci Yan Jiu. 2014 Aug;39(4):272-7.
[Effect of electroacupuncture intervention on autophagy pathway in APP 695 V 717 I transgenic mice].




Neural Regen Res. 2014 Jun 1;9(11):1163-8. doi: 10.4103/1673-5374.135319.
Acupuncture at the Taixi (KI3) acupoint activates cerebral neurons in elderly patients with mild cognitive impairment.
Chen S1, Xu M2, Li H3, Liang J4, Yin L2, Liu X4, Jia X5, Zhu F5, Wang D5, Shi X4, Zhao L6.
Author information



PLoS One. 2014 Nov 26;9(11):e113126. doi: 10.1371/journal.pone.0113126. eCollection 2014.
EGb761 Provides a Protective Effect against Aβ1-42 Oligomer-Induced Cell Damage and Blood-Brain Barrier Disruption in an In Vitro bEnd.3 Endothelial Model.
Wan WB1, Cao L2, Liu LM3, Kalionis B4, Chen C5, Tai XT6, Li YM3, Xia SJ7.



Physiol Behav. 2014 Dec 3. pii: S0031-9384(14)00603-9. doi: 10.1016/j.physbeh.2014.12.001. [Epub ahead of print]
Hippocampal cAMP/PKA/CREB is Required for Neuroprotective Effect of Acupuncture.
Li QQ1, Shi GX1, Yang JW1, Li ZX1, Zhang ZH1, He T1, Wang J1, Liu LY1, Liu CZ2.



Zhen Ci Yan Jiu. 2014 Dec;39(6):431-6.
[Effect of electroacupuncture pretreatment on apoptotic neurons and expression of GRP 78 and GADD 153 in the hippocampus in rats with global cerebral ischemia/reperfusion injury].


Evid Based Complement Alternat Med. 2015;2015:393569. doi: 10.1155/2015/393569. Epub 2015 Feb 25.
Electroacupuncture Suppressed Neuronal Apoptosis and Improved Cognitive Impairment in the AD Model Rats Possibly via Downregulation of Notch Signaling Pathway.


Zhen Ci Yan Jiu. 2015 Feb;40(1):6-12.
[Effects of scalp-acupuncture on astrocyte apoptosis in hippocampal CA 1 region in rats with vascular dementia].
[Article in Chinese]
Tian WJ, Huang LN, Wang RH, An JM, Zhang M.



2014 Dec;29(8):739-48. doi: 10.1177/1533317514536600. Epub 2014 Jun 6.
Acupuncture stimulation of Taichong (Liv3) and Hegu (LI4) modulates the default mode network activity in Alzheimer's disease.
Liang P1, Wang Z2, Qian T3, Li K4.



Am J Alzheimers Dis Other Demen.
2015 Apr 28;15(1):133. [Epub ahead of print]
Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.
Li F1,2, Yan CQ3,4, Lin LT5,6, Li H7,8, Zeng XH9,10, Liu Y11,12, Du SQ13, Zhu W14, Liu CZ15.



BMC Complement Altern Med.
2015 Jun;94(22):e933.
The Effectiveness and Safety of Acupuncture for Patients With Alzheimer Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Zhou J1, Peng W, Xu M, Li W, Liu Z.




Medicine (Baltimore).
2015;2015:310591. doi: 10.1155/2015/310591. Epub 2015 Jul 30.
Discovery of Acupoints and Combinations with Potential to Treat Vascular Dementia: A Data Mining Analysis.
Feng S1, Ren Y1, Fan S2, Wang M1, Sun T1, Zeng F1, Li P2, Liang F1.



Evid Based Complement Alternat Med.
Acupunct Med. 2015 Dec 9. pii: acupmed-2015-010865. doi: 10.1136/acupmed-2015-010865. [Epub ahead of print]
Effects of acupuncture at HT7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-FDG-PET study.
Lai X1, Ren J2, Lu Y3, Cui S4, Chen J5, Huang Y2, Tang C1, Shan B6, Nie B6.



Acupunct Med. 2016 Feb 19. pii: acupmed-2015-010894. doi: 10.1136/acupmed-2015-010894. [Epub ahead of print]
Electroacupuncture improves memory and protects neurons by regulation of the autophagy pathway in a rat model of Alzheimer's disease.
Guo HD1, Zhu J1, Tian JX1, Shao SJ1, Xu YW2, Mou FF1, Han XJ1, Yu ZH3, Chen JL3, Zhang DY4, Zhang LS1, Cui GH5.
Neuroreport. 2015 Jan 7;26(1):6-12. doi: 10.1097/WNR.0000000000000295.
Increasing functional connectivity of the anterior cingulate cortex during the course of recovery from Bell's palsy.
Hu S1, Wu Y, Li C, Park K, Lu G, Mohamed AZ, Wu H, Xu C, Zhang W, Wang L, Yang J, Qiu B.
Author information


Abstract
Bell's palsy (BP), a unilateral and idiopathic palsy of the facial nerve, is a common disorder generally followed by a good natural recovery. The aim of this study was to investigate the relationship between the functional connectivity of the anterior cingulate cortex (ACC) and the recovery process of BP. Thirty-seven healthy volunteers and 67 patients were studied by functional MRI (fMRI). The seed regions of bilateral ACC were first extracted from the task-state fMRI data of healthy participants performing the task of mouth opening and closing. The connectivity of bilateral ACC was calculated from resting-state fMRI data of patients in whom only resting-state fMRI data were collected. The correlation between the strength of ACC's connectivity with the duration (time course of disease) was computed by analysis of covariance. It was found that the functional connectivity of the ACC ipsilateral to the lesioned side was enforced as the duration increased. The enforced brain areas included the sensorimotor areas and the ACC contralateral to the palsy. It was suggested that enforced functional connectivity of ACC might be related to cortical reorganization, which is important in the process of BP recovery.












Mol Med Rep. 2013 May;7(5):1516-22. doi: 10.3892/mmr.2013.1392. Epub 2013 Mar 22.
Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.
Feng X, Yang S, Liu J, Huang J, Peng J, Lin J, Tao J, Chen L.
Source
College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China.
Abstract
Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.




Acupunct Electrother Res. 2012;37(2-3):89-101.
Acute effects of electro-acupuncture (EA) on hippocampal long term potentiation (LTP) of perforant path-dentate gyrus granule cells synapse related to memory.
He X, Yan T, Chen R, Ran D.
Source
Dept. of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.
Abstract
Acupuncture, a traditional Chinese therapeutic method, has been widely used in clinical practice to treat diseases such as stroke, Bell's palsy, Alzheimer disease, Parkinson diseases, dysmenorrhea and chronic pain. Mounting lab data had suggested that electro-acupuncture could alleviate dementia and restore long term potentiation of hippocampus in rat. Clinical data also indicated that electro-acupuncture could improve electrical activity of brain in vascular dementia patients. However, its biological basis and acute effects on hippocampal long term potentiation (LTP) remain not well understood. Therefore, we sought to investigate whether acute electro-acupuncture (acupoints: ST36 and SP6; continuous wave, 2 mV, 2Hz; lasted 20 min) could enhance LTP of perforant path-dentate gyrus granule cells in anesthetized rat and explore its underlying mechanisms. We found that electro-acupuncture could significantly increase PS2/PS 1 in pair pulse test (P <0.05, inter-pulse interval: 20ms and 90ms). When compared to control group, electro-acupuncture could significantly enhance LTP to about 234% which was about 143% of that in control group (P <0.05). It suggested that electro-acupuncture could modulate the function of interneurons in hippocampus hence increase LTP.




Zhongguo Zhen Jiu. 2012 Aug;32(8):726-30.
[Effects of electroacupuncture on the function of respiration chain in hippocampal mitochondria of SAMP8 mice ].
[Article in Chinese]
Dong WG, Lin L, Wang F, Chen Y, Chen CY, Xie YC, Chen Y.
Source
College of Integrated Chinese and Western Medicine, Fujian University of TCM, Fuzhou 350108, China.
Abstract
OBJECTIVE:
from the perspective of mitochondria.
METHODS:
Tweleve SAMP8 mice aged 8 months were randomly divided into a model group (n = 6) and an electroacupuncture group (n = 6), and six SAMR1 mice aged 8 months were selected as a control group. The electroacupuncture group was treated with electroacupuncture at "Baihui" (GV 20), "Dazhui" (GV 14), "Shenshu" (BL 23) and "Taixi" (KI 3) for 20 min, once each day, 10 days for a course, and lasted for 3 courses. The other two groups were grasped and fixed in the same way at the same time without the other treatment. After the end of treatment, the learning and memory abilities of the mice were measured by Morris water maze, the activity of hippocampal mitochondrid respiratory chain enzyme complex was performed by spectrophotometry, and the levels of adenosine triphosphate (ATP) were detected by a reverse-phase high performance liquid chromatography (HPLC) method.
RESULTS:
Compared with the control group, the average escape latency significantly lengthened, the residence time on the plateau phase shortened, the activity of respiratory chain enzyme complexe I, II, III, and IV was decreased, and ATP concentration was decreased in the model group. Compared with the model group, the average escape latency significantly shortened, the residence time on the plateau phase lengthened, the activity of hippocampal mitochondrid respiratory chain complexes I, II, III, and IV was significantly increased, and ATP concentration was increased in the electroacupuncture group.
CONCLUSION:
Electroacupuncture can increase the activity of hippocampal mitochondrid respiratory chain enzyme complexe and ATP concentration and improve mitochondrial function, which may be one of underlying mechanisms of electroacupuncture in treatment of AD.




Acupunct Med. 2012 Dec;30(4):339-45. doi: 10.1136/acupmed-2012-010180. Epub 2012 Sep 12.
Acupuncture improves cognitive deficits and increases neuron density of the hippocampus in middle-aged SAMP8 mice.
Li G, Zhang X, Cheng H, Shang X, Xie H, Zhang X, Yu J, Han J.
Source
Department of Rehabilitation Medicine, First People’s Hospital of Chenzhou, Chenzhou, Hunan Province, China.
Abstract
OBJECTIVES:
To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing.
METHODS:
Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique.
RESULTS:
The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (-24%), CA3 (-18%) and DG (-28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group.
CONCLUSIONS:
Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.




J Altern Complement Med. 2012 Apr;18(4):387-93. doi: 10.1089/acm.2010.0205.
Capturing amplitude changes of low-frequency fluctuations in functional magnetic resonance imaging signal: a pilot acupuncture study on NeiGuan (PC6).
Zhang G, Yin H, Zhou YL, Han HY, Wu YH, Xing W, Xu HZ, Zuo XN.
Source
Department of Acupuncture, No. 1 Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China.
Abstract
OBJECTIVES:
This study aims to examine amplitude changes of low-frequency oscillations (fALFF) in the blood-oxygen level-dependent (BOLD) signal associated with acupuncture on NeiGuan (PC6).
EXPERIMENTAL DESIGN:
Ten (10) healthy adults participated in a functional magnetic resonance imaging (i.e., nuclear medicine; fMRI) study. During the brain-imaging procedure, the participants were instructed to lie quietly; they did not perform any cognitive task.
MAIN OUTCOME MEASURES:
Three (3) fMRI scans were conducted for each participant: a first resting-state scan (R1), a stimulating-acupoint scan (AP), and a second resting-state scan (R2) after AP. Individual fALFF maps were calculated for each scan.
RESULTS:
During R1, consistent with previous studies, the default network regions showed significantly detectable fALFF amplitudes. Acupuncture on PC6 increased fALFF amplitudes within the anterior cingulate cortex (ACC), occipital fusiform gyrus, posterior cingulate cortex, and precuneus (PCC/PCU). In contrast, during R2, fALFF within PCC is still significantly higher than R1 while ACC and cerebellum showed decreased fALFF.
CONCLUSIONS:
These findings imply that stimulating PC6 can change the amplitude of the intrinsic cortical activity of the brain. In particular, a continuous and temporally consistent effect of acupuncture within PCC not the common brain circuit of pain including ACC and cerebellum was observed. Considering the cognitive functions and deficits of the relevant areas in mild cognitive impairment and Alzheimer disease, acupuncture on PC6 could potentially affect both psychiatric and neurological disorders. Thus, stimulating PC6 may be a candidate method for improving cognitive impairment.








Magn Reson Imaging. 2012 Jun;30(5):672-82. doi: 10.1016/j.mri.2012.01.003. Epub 2012 Mar 27.
FMRI connectivity analysis of acupuncture effects on the whole brain network in mild cognitive impairment patients.
Feng Y, Bai L, Ren Y, Chen S, Wang H, Zhang W, Tian J.
Source
Medical Image Processing Group, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
Abstract
The increased risk for the elderly with mild cognitive impairment (MCI) to progress to Alzheimer's disease makes it an appropriate condition for investigation. While the use of acupuncture as a complementary therapeutic method for treating MCI is popular in certain parts of the world, the underlying mechanism is still elusive. We sought to investigate the acupuncture effects on the functional connectivity throughout the entire brain in MCI patients compared to healthy controls (HC). The functional magnetic resonance imaging experiment was performed with two different paradigms, namely, deep acupuncture (DA) and superficial acupuncture (SA), at acupoint KI3. We first identified regions showing abnormal functional connectivity in the MCI group compared to HC during the resting state and subsequently tested whether these regions could be modulated by acupuncture. Then, we made the comparison of MCI vs. HC to test whether there were any specific modulatory patterns in the poststimulus resting brain between the two groups. Finally, we made the comparisons of DA vs. SA in each group to test the effect of acupuncture with different needling depths. We found the temporal regions (hippocampus, thalamus, fusiform gyrus) showing abnormal functional connectivity during the resting state. These regions are implicated in memory encoding and retrieving. Furthermore, we found significant changes in functional connectivity related with the abnormal regions in MCI patients following acupuncture. Compared to HC, the correlations related with the temporal regions were enhanced in the poststimulus resting brain in MCI patients. Compared to SA, significantly increased correlations related with the temporal regions were found for the DA condition. The enhanced correlations in the memory-related brain regions following acupuncture may be related to the purported therapeutically beneficial effects of acupuncture for the treatment of MCI. The heterogeneous modulatory patterns between DA and SA may suggest that deep muscle insertion of acupuncture is necessary to achieve the appreciable clinical effect.
Copyright © 2012 Elsevier Inc. All rights reserved.




J Tradit Chin Med. 2011 Sep;31(3):178-81.
Clinical research on comprehensive treatment of senile vascular dementia.
Chen LP, Wang FW, Zuo F, Jia JJ, Jiao WG.
Source
General Hospital of People's Liberation Army, Beijing 100853, China. lipingschen@yahoo.com.cn
Abstract
OBJECTIVE:
To observe the curative effect of combined Chinese medicine, acupuncture and rehabilitation therapy on vascular dementia (VD), and to compare the Western medicine piracetam.
METHODS:
Total 134 VD patients screened in reference to the standard for VD diagnosis in DSM-IV were randomly divided into a Chinese medicine plus rehabilitation group (32 cases), a Chinese medicine plus acupuncture group (33 cases), a Chinese medicine and acupuncture plus rehabilitation group (37 cases) and a Western medicine piracetam group (32 cases). Mini Mental State Examination (MMSE) and Bless Behavior Scale (BBS) were used to assess changes in intelligence disorder before treatment and after 12-week treatment.
RESULTS:
BBS score, living ability and daily habit were enhanced after treatment in all groups. Cognitive function and behavioral ability were improved with similar total curative effects in all the 4 groups. Directional ability and short-term memory ability were significantly enhanced after treatment (P < 0.05) in both the Chinese medicine plus rehabilitation group and the Chinese medicine plus acupuncture group groups. Living ability was significantly improved after treatment in the Chinese medicine and acupuncture plus rehabilitation group (P < 0.01). However, no obvious difference was shown before and after treatment in the piracetam group.
CONCLUSION:
The improvement of living ability in the comprehensive treatment group is better than that in the other groups. Chinese medicine and acupuncture plus rehabilitation treatment can improve intelligence and living ability of senile VD patients.




Zhen Ci Yan Jiu. 2011 Apr;36(2):90-4.
[Effect of "Xiusanzhen" on hippocampal muscarinic cholinergic receptor activity in Alzheimer disease rats].
[Article in Chinese]
Yang XH, Liu ZB, Niu WM, Niu XM.
Source
Department of Medical Technology, Shaanxi College of Chinese Medicine, Xianyang 712046, China. yxh1.o@163.com
Abstract
OBJECTIVE:
To explore the effect of "Xiusanzhen" [electroacupuncture (EA) of bilateral "Yingxiang" (LI 20) and "Yintang" (EX-HN 3)] on activities of hippocampal muscarinic cholinergic receptor (mAChR) and the involved neural path in Alzheimer Disease(AD)rats.
METHODS:
Forty Sprague Dawley rats were randomly divided into normal control, model, olfactory nerve severing (ONS)-EA of "Xiusanzhen" (ONS-EA) and EA of "Xiusanzhen" (EA) groups. AD model was established by intra-hippocampal injection (AP: 3.5 mm, L:2 mm, H: -2.8 mm) of Abeta(1-40) starch-like peptide (10 microg/2 microL) under the aid of a microsyringe installed in a brain stereotaxis instrument. For rats of the ONS-EA group, the olfactory nerve was severed by using a surgical knife after drilling a hole on the skull (5 mm anterior to the bregma, L, R: 2 mm). The mAChR density, and its maximum binding capacity (Bmax) and dissociation constant (Kd) of the hippocampus tissue were measured by using radio-ligand binding analysis and Lowry's microamount protein assay.
RESULTS:
In comparison with the normal control group, the hippocampal mAChR density and its Bmax in the model group were decreased remarkably (P < 0.05), while the Kd of M-receptor in the model group was increased remarkably (P < 0.05). In comparison with the model group, hippocampal mAChR density and its Bmax in the EA group were up-regulated obviously (P < 0.05), while the Kd of mAChR in the EA group was down-regulated significantly (P < 0.05). No significant differences were found between the model and ONS-EA groups in mAChR density and its Bmax and Kd (P > 0.05).
CONCLUSION:
"Xiusanzhen"-EA can effectively up-regulate hippocampal mAChR density and Bmax and down-regulate Kd of M-receptor of hippocampus in AD rats, which is dependent on the intact olfactory nerve pathway.


2

Zhen Ci Yan Jiu. 2011 Feb;36(1):7-11.
[Effect of "Xiusanzhen"on expression of hippocampal Bcl-2 and Bax proteins in Alzheimer disease rats].
[Article in Chinese]
Liu ZB, Niu WM, Yang XB, Niu XM, Yuan W.
Source
Department of Acu-moxibustion and Tuina, Shaanxi College of Chinese Medicine, Xianyang 712046, China. lzb210396@163.com
Abstract
OBJECTIVE:
To observe the effect of electroacupuncture (EA) of "Xiusanzhen" [3 acupoints, i.e., bilateral "Yingxiang" (LI 20) and "Yintang" (EX-HN 3)] on expression of B-cell lymphoma/leukemia-2 (Bcl-2, an antiapoptosis protein) and Bax (a protein for promoting apoptosis) in the hippocampus in Alzheimer disease (AD) rats, so as to explore its clinical mechanisms underlying relieving AD.
METHODS:
A total of 40 Sprague Dawley rats were randomly divided into normal control, AD model, EA and olfactory nerve transaction(ONT) + EA groups, with 10 rats in each. AD model was established by injection of beta-amyloid (Abeta)(1-40) (2 microL containing 10 microg) into the hippocampus (Bregma: 3.5 mm, L: 2.0 mm, H: -2.8 mm below dura), and the ON was sectioned by using a fine needle. EA (80-100 Hz, 1-3 mA) was applied to bilateral LI 20 and EX-HN 3 for 10 min, once daily (except Saturdays and Sundays) for 6 weeks. The expression of Bcl-2 and Bax of hippocampus was measured by immunohisto-chemistry.
RESULTS:
Compared with the normal control group, the expression of Bcl-2 of hippocampus was significantly lower in the AD model group (P<0.05), and that of Bax in AD model group was much higher (P<0.01). In comparison with the model group, the expression of hippocampal Bcl-2 was up-regulated significantly (P<0.01), and that of hippocampal Bax protein downregulated considerably in the EA group (P<0.01). No significant differences were found between AD model and ONT + EA groups in the expression of hippocampal Bcl-2 and Bax proteins (P>0.05), suggesting a necessary premise condition for EA in regulating hippocampal Bcl-2 and Bax expression.
CONCLUSION:
"Xiusanzhen" can regulate the expression of hippocampal Bcl-2 and Bax proteins in AD rats, which may contribute to its clinical effect in relieving AD, and the therapeutic effect depends on the integrity of the olfactory nerve pathway.




Front Med Biol Eng. 2002;11(4):237-47.
A study on the rehabilitation of cognitive function and short-term memory in patients with Alzheimer's disease using transcutaneous electrical nerve stimulation.
Guo Y, Shi X, Uchiyama H, Hasegawa A, Nakagawa Y, Tanaka M, Fukumoto I.
Source
Institute of Biomedical Engineering, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka 940-2188, Japan. guoyi@stn.nagaokaut.ac.jp
Abstract
In some previous studies, transcutaneous electrical nerve stimulation (TENS) to the back was shown to improve non-verbal short-term and long-term memory as well as verbal fluency in patients in the early stage of Alzheimer's disease (AD). Moreover, the patients' physical, social and affective functions were also improved. In this study, the effects of TENS applied to the face were studied in patients with mild and severe AD. Fourteen patients with probable AD were used as subjects. To evaluate the effects of treatment, the subjects underwent two kinds of neuropsychological tests as well as a pupillary light reflex test. The pupillary light reflex test was chosen because it has been proven to show poorer results in cases of senile dementia. These three tests were carried out before the treatment, immediately after the treatment and 6 months after the treatment. Improvements were seen in subjects in the TENS groups and the effects of treatment were more significant in mild AD patients than in severe AD patients. However, the improvements were not maintained 6 months after the treatment. The possible mechanisms underlying the beneficial effects of TENS in AD patients are discussed in this paper.


PLoS One. 2012;7(8):e42730. doi: 10.1371/journal.pone.0042730. Epub 2012 Aug 20.
Effect of acupuncture in mild cognitive impairment and Alzheimer disease: a functional MRI study.
Wang Z, Nie B, Li D, Zhao Z, Han Y, Song H, Xu J, Shan B, Lu J, Li K.
Source
Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Abstract
We aim to clarify the mechanisms of acupuncture in treating mild cognitive impairment (MCI) and Alzheimer disease (AD) by using functional magnetic resonance imaging (fMRI). Thirty-six right-handed subjects (8 MCI patients, 14 AD patients, and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all the subjects. MRI data acquisition was performed on a SIEMENS verio 3-Tesla scanner. The fMRI study used a single block experimental design. We first acquired the baseline resting state data in the initial 3 minutes; we then acquired the fMRI data during the procession of acupuncture stimulation on the acupoints of Tai chong and Hegu for the following 3 minutes. Last, we acquired fMRI data for another 10 minutes after the needle was withdrawn. The preprocessing and data analysis were performed using the statistical parametric mapping (SPM8) software. Then the two-sample t-tests were performed between each two groups of different states. We found that during the resting state, brain activities in AD and MCI patients were different from those of control subjects. During the acupuncture and the second resting state after acupuncture, when comparing to resting state, there are several regions showing increased or decreased activities in MCI, AD subjects compared to normal subjects. Most of the regions were involved in the temporal lobe and the frontal lobe, which were closely related to the memory and cognition. In conclusion, we investigated the effect of acupuncture in AD and MCI patients by combing fMRI and traditional acupuncture. Our fMRI study confirmed that acupuncture at Tai chong (Liv3) and He gu (LI4) can activate certain cognitive-related regions in AD and MCI




Zhongguo Zhen Jiu. 2010 Dec;30(12):1007-10.
[Effects of electroacupuncture on expression of Abeta positive cells of the hippocampus and SOD activity in rats with streptozocin-Alzheimer's disease].
[Article in Chinese]
Zhang P, Guan SS, Jiang GH.
Source
Heilongjiang University of TCM, Harbin 150040, China.
Abstract
OBJECTIVE:
To investigate the possible mechanism of the electroacupuncture for improvement of learning and memory in rats of Alzheimer's disease (AD).
METHODS:
Sixty Wistar rats were randomly divided into a normal group, a normal saline group, a model group, a western medication group and an electroacupuncture group, 12 rats in each group. The AD rat model was established by injecting Streptozocin (STZ) into lateral cerebral ventricle, except the rats in the normal saline group injecting Normal Saline with the same dose and in normal group with no injection. The western medication group was treated with intragastric administration of Memantine, and in the electroacupuncture group, the electroacupuncture was given at "Baihui" (GV 20), "Dazhui" (CV 14), "Taixi" (KI 3), "Shenshu" (BL 23), "Zusanli" (ST 36), once each day, 7 days for a course, and lasted for 4 courses. The other three groups were fed in routine way and without any treatment. The learning and memory ability was assessed by Morris water maze and the expression of Abeta positive cells of the hippocampus and superoxide dismutase (SOD) activity were determined by immunohistochemistry and visible spectrophotometer colorimetry.
RESULTS:
Compared with the normal group and the normal saline group, the Abeta protein expression was significantly increased in the model group (both P < 0.01), and the SOD activity was obviously decreased (both P < 0.01). After treatment, as compared with the model group, the Abeta protein expression was significantly decreased (both P < 0.01), and the SOD activity was obviously increased (both P < 0.01) in the electroacupuncture group and western medication group.
CONCLUSION:
Electroacupuncture treatment can reduce the Abeta protein expression and increase the SOD activity of the hippocampus so as to improve learning and memory ability in the AD rats.




Zhongguo Zhen Jiu. 2009 Feb;29(2):133-6.
[Effects of electroacupuncture on learning and memory ability and glial cells of the hippocampus in the rat of Alzheimer disease].
[Article in Chinese]
Zhu SX, Sun GJ.
Source
TCM Department, College of Medical Sciences, Jianghan University, Wuhan 430065, Hubei, China.
Abstract
OBJECTIVE:
To study on the mechanism of electroacupuncture for treatment of Alzheimer disease (AD).
METHODS:
SD rats were randomly divided into a normal group, a sham operation group, a model group and an electroacupuncture group, 12 rats in each group. The AD rat model was prepared by microinjection of amyloid-beta protein (Abeta1-40) into the Meynert nucleus. In the electroacupuncture group, electroacupuncture was given at "Baihui" (GV 20), "Taixi" (KI 3), "Zusanli" (ST 36). The learning and memory ability was assessed by Morris water maze and the glial cell activity in the hippocampus was determined by immunohistochemistry.
RESULTS:
Compared with the normal group, the glial cell in the hippocampus was activated with increase of the number, and the learning and memory ability reduced in the model group (P < 0.01). After treatment, as compared with the model group, the number of the activated glial cells was reduced and the learning and memory ability was improved in the electroacupuncture group (P < 0.01).
CONCLUSION:
Electroacupuncture treatment can decrease the number of activated glial cells so as to protect the neurons, improving the learning and memory ability in the AD rat.



Acupunct Electrother Res. 2008;33(1-2):9-17.
Effect of acupuncture given at the HT 7, ST 36, ST 40 and KI 3 acupoints on various parts of the brains of Alzheimer' s disease patients.
Zhou Y, Jin J.
Source
Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
Abstract
In this study, we explore various regions of the brains of Alzheimer' s Disease (AD) patients before and after acupuncture treatment of acupoints in the brain in order to determine the effect, if any, of acupuncture on AD. Twenty-six patients with clinically-diagnosed AD underwent functional magnetic resonance imaging (fMRI) while undergoing acupuncture at the four acupoints of Shenmen (HT 7), Zusanli (ST 36), Fenglong (ST 40) and Taixi (KI 3). fMRI Block design paradigm was chosen by electroacupumcture interval stimulation, and the data of fMRI were analyzed by Statistical Parametric Mapping (SPM 99). The result demonstrated that there were right main hemisphere activations (temporal lobe, such as hippocampal gyrus, insula, and some area of parietal lobe) and left activated regions (temporal lobe, parietal lobule, some regions of cerebellum). The activated regions induced by these acupoints were consistent with impaired areas in brain for AD patients, which were closely correlated with the cognitive function (memory, reason, language, executive, etc.). The present study provided the strong evidence that acupuncture had a potential effect on AD, and in partial revealed the mechanism.




[Clinical observation on catgut implantation at acupoint for treatment of Alzheimer's disease].
[Article in Chinese]
Zhou YL, Jia JP.
Source
Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
Abstract
OBJECTIVE:
To observe clinical therapeutic effect of catgut implantation at acupoint on Alzheimer's disease (AD).
METHODS:
Twenty-six cases with mild-moderate AD were divided into an acupoint catgut implantation group and a control group by sample-paired method. The acupoint catgut implantation group were treated with cat-gut implantation at Shenmen (HT 7), Zusanli (ST 36), Fenglong (ST 40) and Taixi (KI 3), and the control group with the same manipulation at the same acupoints with no catgut implanted, once each month, for 6 months. Mini-Mental State Examination (MMSE), Activity of Daily Living (ADL) and Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-Cog) scores were recorded before and after treatment and analyzed statistically.
RESULTS:
After treatment, the score of MMSE significantly increased (P < 0.01), the score of ADAS-Cog significantly decreased (P < 0.01) and the score of ADL did not significantly change in the acupoint catgut implantation group; compared with the control group, the score of MMSE in the acupoint catgut implantation significantly increased (P < 0.01), the score of ADAS-Cog significantly decreased (P < 0.05) and the score of ADL did not significantly change in the acupoint catgut implantation.
CONCLUSION:
Acupoint catgut implantation therapy increases cognitive function of the patient of AD, which provides a new therapeutic method for aged AD.




Zhongguo Zhen Jiu. 2005 Jun;25(6):390-2.
[Clinical observation on acupuncture combined with music for treatment of Alzheimer disease].
[Article in Chinese]
Liu G, Yuan LX.
Source
College of Acupuncture and Massage, Guangzhou University of TCM, Guangdong 510405, China. cnlgtcm@163.com
Abstract
OBJECTIVE:
To find the method for increasing clinical therapeutic effect on Alzheimer disease (AD).
METHODS:
The patients of AD meeting American NINCDS-ADRDA Criteria were randomly divided into group A and group B. The group A (n = 21) were treated with acupuncture for 10 courses, 10 sessions constituting one course; and the group B (n = 20) were treated with combination of acupuncture and music therapy. The acupuncture method was the same as the group A and the music therapy was given for 20 sessions, once every 5 days. After treatment, their effectiveness were evaluated with the Mini-Mental State Examination (MMSE) and Activities of Daily Living (ADL).
RESULTS:
After treatment, the scores for MMSE increased significantly (P < 0.05) and the scores for ADL decreased significantly (P < 0.05) in the both groups, and the therapeutic effect in the group A was better than the group B (P < 0.05).
CONCLUSION:
Acupuncture combined with music therapy can increase the therapeutic effect on AD.




J Tradit Chin Med. 2013 Feb;33(1):46-50.
Clinical observation on effect of scalp electroacupuncture for mild cognitive impairment.
Zhang H, Zhao L, Yang S, Chen Z, Li Y, Peng X, Yang Y, Zhu M.
Source
Department of Acupuncture and Tuina, Chengdu University of Tranditional Chinese Medicine, Chengdu 610075, China. hzhang0123@foxmail.com
Abstract
OBJECTIVE:
To evaluate the therapeutic effect of scalp electroacupuncture for mild cognitive impairment (MCI) in the early stage.
METHODS:
Two hundred and thirty three MCI patients were randomly divided into three groups: the drug group, the scalp electroacupuncture group, and the syndrome differentiation group. For the scalp electroacupuncture group, the points of Baihui (DU 20), Sishecong (EX-HN1), Fengchi (GB 20), and Shenting (DU 24) were selected. For the syndrome differentiation group, specific acupoints were added on the basis of syndrome differentiation and according to the scale for the differentiation of syndromes in vascular dementia (SDSVD) beside the acupoints used in the scalp electroacupuncture group. For the drug group, nimodipine was orally administered. Each patient was treated for two courses, eight weeks. The score differences in mini-mental state examination (MMSE), picture recognition, and clock drawing test were observed before and after the treatment.
RESULTS:
After treatment, the score differences in MMSE and clock drawing test were of obvious statistical significance among three groups (P < 0.01, P < 0.05). The score differences in picture recognition were of extremely statistical significance between the scalp electroacupuncture group and the syndrome differentiation group (P < 0.01), while the difference was not found in the drug group (P > 0.05). There were statistical significant differences in therapeutic effects between the scalp electroacupuncture group and the drug group, and between the syndrome differentiation group and the drug group (P < 0.05), while no statistical difference was found between scalp electroacupuncture group and the syndrome differentiation group (P > 0.05).
CONCLUSION:
All the three therapies may improve the cognitive function of MCI patients. The therapeutic effects in the scalp electroacupuncture and syndrome differentiation groups were basically the same, but superior to nimodipine.




Zhongguo Zhen Jiu. 2012 Sep;32(9):779-84.
[Mild cognitive impairment disease treated with electroacupuncture: a multi-center randomized controlled trial].
[Article in Chinese]
Zhao L, Zhang FW, Zhang H, Zhao Y, Zhou B, Chen WY, Zhu MJ.
Source
Chengdu University of TCM, College of Acupuncture-Moxibustion and Massage, Chengdu 610075, Sichuan Province, China. zhaoling@cdutcm.edu.cn
Abstract
OBJECTIVE:
To verify the clinical efficacy on mild cognitive impairment (MCI) treated with electroacupuncture (EA) intervention based on the principle as "promoting the circulation of the Governor Vessel and regulating the marrow" and plan to provide the A-grade evidence of the evidence-based medicine for the clinical treatment of this disease with acupuncture and moxibustion.
METHODS:
The multi-center randomized controlled trial (RCT) was adopted. One hundred and ninety-two cases of MCI were randomized into an EA group and a nimodipine group, 96 cases in each one. In the EA group, EA was applied to Shenting (GV 24), Baihui (GV 20), Sishen cong (EX-HN 1) and Fengchi (GB 20), once every other day. In the nimodipine group, Nimodipine was pre scribed for oral administration. Four weeks constituted one course, the treatment of 8 weeks was required. The minimum mental state examination (MMSE) and the graphic recognition test (GRT) were applied before and in the 1st and 2nd session of treatment separately. The follow-up visit of MMSE scale was provided in the 1st, 3rd and 6th months after treatment separately.
RESULTS:
The total effective rate was 50.0% (47/94) in the EA group, which was superior to 34.4% (32/93) in the nimodipine group (P < 0.05). At the end of the 1st session treatment, the differences in MMSE total score and the cognitive, memory and speech dimensional scores were not significant statistically between two groups (all P > 0.05). At the end of the 2nd session treatment, the MMSE total score and the cognitive, memory, visual-space skill dimensional scores were improved in comparison before treatment (all P < 0.05). The results in the EA group were superior to those in the nimodipine group (all P < 0.05). But the difference in the speech dimensional score was not significant statistically between the two groups (P > 0.05). In the EA group, the GRT score was improved significantly after 2 sessions of treatment as compared with that before treatment (P < 0.01) and was superior to that in the nimodipine group (P < 0.05). In the 1st, 3rd and 6th month after treatment, the MMSE scale total scores were different significantly in statistics between the two groups (all P < 0.01). The long-term efficacy in the EA group was superior to that in the nimodipine group.
CONCLUSION:
Both of the EA therapy based on the principle as "promoting the circulation of the Governor Vessel and regulating the marrow" and the nimodipine program improve significantly the cognitive function of MCI patients. Compared with the nimodipine program, the EA therapy improves the comprehensive cognitive and the short-term memory abilities much more significantly and is especially advantageous at improving cognitive, memory and visual-space skill dimensions for MCI patients. In the half a year follow-up visit after the end of treatment, the long-term efficacy of EA is better than that of Nimodipine.




Evid Based Complement Alternat Med. 2013;2013:127271. doi: 10.1155/2013/127271. Epub 2013 Aug 19.
Multivariate granger causality analysis of acupuncture effects in mild cognitive impairment patients: an FMRI study.
Chen S, Bai L, Xu M, Wang F, Yin L, Peng X, Chen X, Shi X.
Source
Baoan Hospital, Southern Medical University, Shenzhen 518101, China.
Abstract
Evidence from clinical reports has indicated that acupuncture has a promising effect on mild cognitive impairment (MCI). However, it is still unknown that by what way acupuncture can modulate brain networks involving the MCI. In the current study, multivariate Granger causality analysis (mGCA) was adopted to compare the interregional effective connectivity of brain networks by varying needling depths (deep acupuncture, DA; superficial acupuncture, SA) and at different cognitive states, which were the MCI and healthy control (HC). Results from DA at KI3 in MCI showed that the dorsolateral prefrontal cortex and hippocampus emerged as central hubs and had significant causal influences with each other, but significant in HC for DA. Moreover, only several brain regions had remarkable causal interactions following SA in MCI and even few brain regions following SA in HC. Our results indicated that acupuncture at KI3 at different cognitive states and with varying needling depths may induce distinct reorganizations of effective connectivities of brain networks, and DA at KI3 in MCI can induce the strongest and more extensive effective connectivities related to the therapeutic effect of acupuncture in MCI. The study demonstrated the relatively functional specificity of acupuncture at KI3 in MCI, and needling depths play an important role in acupuncture treatments.




J Acupunct Meridian Stud. 2013 Oct;6(5):247-51. doi: 10.1016/j.jams.2013.07.001. Epub 2013 Jul 17.
Laser acupuncture improves memory impairment in an animal model of Alzheimer's disease.
Sutalangka C, Wattanathorn J, Muchimapura S, Thukham-Mee W, Wannanon P, Tong-Un T.
Source
Department of Physiology (Neuroscience Program), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Integrative Complementary Alternative Medicine Research and Development Group, Khon Kaen University, Khon Kaen, Thailand.
Abstract
The burden of Alzheimer's disease is continually rising globally, especially in the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy is still very limited. Because the effect of acupuncture at HT7 can improve learning and memory, the beneficial effect of laser acupuncture, a noninvasive form of acupuncture, at HT7 on memory improvement in patients with Alzheimer's disease has been a focus of research. To elucidate this issue, we used AF64A, a cholinotoxin, to induce memory impairment in male Wistar rats, which weighed 180-220 g. Then, the animals were treated with laser acupuncture either at HT7 or at a sham acupoint once daily for 10 minutes for a period of 14 days. Spatial memory assessments were performed at 1, 7, and 14 days after AF64A administration and at the end of the experiment, and the changes in the malondialdehyde (MDA) level and in the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in the hippocampus were recorded. The results showed that laser acupuncture significantly suppressed AChE activity in the hippocampus. Although laser acupuncture enhanced SOD and CAT activities, no reduction in MDA level in this area was observed. Therefore, laser acupuncture at HT7 is a potential strategy to attenuate memory impairment in patients with Alzheimer's disease. However, further research, especially on the toxicity of laser acupuncture following repetitive exposure, is essential.
Copyright © 2013. Published by Elsevier B.V.




J Tradit Chin Med. 2013 Aug;33(4):461-7.
Ear therapy and massage therapy in the elderly with dementia: a pilot study.
Rodríguez-Mansilla J, González-López-Arza MV, Varela-Donoso E, Montanero-Fernández J, Jiménez-Palomares M, Garrido-Ardila EM.
Source
Department of Medical-Surgical Therapy, Medicine Faculty, Extremadura University, Badajoz 06006, Spain. jrodman@unex.es
Abstract
OBJECTIVE:
To assess the impact of massage versus ear acupuncture on behavior and participation in occupational therapy of dementia patients.
METHODS:
We performed a controlled, randomized longitudinal trial approved by the Bioethics Commission of the University of Extremadura. One hundred twenty elderly subjects with dementia institutionalized in residential homes in Extremadura (Spain) received treatment based on massage and ear acupuncture over three months. Behavior alterations, sleep disturbance, and participation in rehabilitation and eating were assessed every month during the three months of intervention, and at one and two months of follow-up after the end of treatment. The assessment was performed through a structured questionnaire with closed format questions done by an occupational therapist not involved in the study.
RESULTS:
There was a statistically significant positive effect of massage and ear acupuncture (P < 0.001) on measured variables in the third month of intervention, which were maintained at two months after completing the treatment (P < 0.021), when compared to the control group.
CONCLUSION:
Massage therapy and ear acupuncture can improve behavior and sleep disturbances, and increase the participation in eating and rehabilitation organized in residential homes, in dementia patients.




Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Dec;33(12):1626-30.
[Treating vascular mild cognitive impairment by acupuncture: a systematic review of randomized controlled trials].
[Article in Chinese]
Zhou L1, Zhang YL2, Cao HJ3, Hu H1.
Author information


Abstract
OBJECTIVE:
To systematically evaluate the effect and safety of acupuncture in the treatment of vascular mild cognitive impairment (VMCI).
METHODS:
Recruited were China National Knowledge Infrastructure Database (CNKI) (1979-2012), Chinese Science and Technology Periodical Database (VIP) (1989-2012), Chinese Biomedical Database (CBM), Wanfang degree and conference papers database (1985-2012), PubMed Database (1966-2012), and The Cochrane Library (Issue 1, 2012). The search date ended in February 2012. Randomized controlled trials (RCTs) by taking acupuncture as the main treatment for VMCI (nonvascular dementia) were collected. Results were measured using at least one internationally recognized evaluation cognitive scale. Two analysts selected the data independently. The assessment of methodological quality was based on the Cochrane Handbook and the data were analyzed by using RevMan 5.1.0 Software. The mean difference (MD) or risk ratio (RR) were taken and graphed with 95% confidence interval (CI).
RESULTS:
Recruited 12 RCTs included a total of 691 cases meeting the inclusion criteria (all of the methodological quality was of B level). Acupuncture combined other therapies was involved in 9 RCTs, with effect compared with that of other therapies. Results of meta-analysis showed, compared with the cognitive function training alone, electroacupuncture (MD 1.59, 95% CI 0.69-2.48, P = 0.0005, 3 studies) or body acupuncture (MD 3.26, 95% CI 1.69-4.83, P < 0.01, 1 study) combined with the cognitive function training could significantly increase the mini-mental state examination (MMSE) score of patients. In comparison to Western medicine, acupuncture could elevate ADAS-Cog score (MD 2.16, 95% CI 1.36-2.95, P < 0.01, 3 studies). In all the studies, adverse event had not been reported.
CONCLUSIONS:
Acupuncture in combination with other therapies could significantly improve cognitive functions. Acupuncture itself appeared to have better therapeutic effects than Western medicine alone.


Neurol Sci. 2013 Jul;34(7):1093-7. doi: 10.1007/s10072-012-1209-4. Epub 2012 Oct 9.
Effect of electroacupuncture on the expression of mTOR and eIF4E in hippocampus of rats with vascular dementia.
Zhu Y1, Zeng Y, Wang X, Ye X.
Author information


Abstract
Clinically, electroacupuncture is proved to be an effective therapy for vascular dementia; however, their mechanisms remain uncertain. The aim of the current study was to investigate the mechanism of electroacupuncture therapy for vascular dementia. One month after a vascular dementia animal model was established by bilateral occlusion of common carotid arteries, electroacupuncture treatment was given at "Baihui" (DU20), "Dazhui" (DU14), and "Shenshu" (BL23). Morris water maze was used to assess the learning and memory ability of rats. Western blot assay was performed to detect the expression of mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) in hippocampus of rats. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression level of mTOR and eIF4E in the electroacupuncture group and sham-operated group was higher than that in the vascular dementia group (P < 0.05). In conclusion, the decreasing expression of mTOR and eIF4E plays important roles in the pathogenesis of vascular dementia. Electroacupuncture improves learning and memory ability by up-regulating expression of mTOR and eIF4E in the hippocampus of vascular dementia rats.
PMID: 23053837 [PubMed - indexed for MEDLINE]




Zhongguo Zhen Jiu. 2014 Feb;34(2):157-62.
[Protective mechanism of acupuncture-moxibustion on hippocampal neuron mitochondria in rats with Alzheimer's disease].
[Article in Chinese]
Sun GJ, Luo L, Du YJ, Kong LH.
Abstract
OBJECTIVE:
To observe effects of acupuncture and moxibustion on ultrastructure and silent information regulator 1 (SIR1) in hippocampal neuron mitochondria in rats with Alzheimer's disease (AD) in order to explore its possible effective mechanism during the process of protecting mitochondria.
METHODS:
Eighty Wistar rats were randomly divided into a normal group, a sham operation group, a model group and an acupuncture group, 20 rats in each one. The AD model was established in the model group and acupuncture group with injection of Amyloid beta Protein Fragment1-14 (Abeta1-42) into the hippocampus. Acupuncture and moxibustion was applied at "Baihui" (GV 20) and "Shenshu" (BL 23) in the acupuncture group, once a day, seven days as a treatment course and totally two course were required. The rest groups were all fed with normal diet, without any treatment. The transmission electron microscopy, immunohistochemistry and immunoblotting technique were respectively adapted to measure ultrastructure and level of STR1 in hippocampal neuron mitochondria in AD rats.
RESULTS:
Compared with the model group, the ultrastructure in hippocampal neuron mitochondria in the acupuncture group was effectively improved. The average optical density of SIR1 in hippocampus was 0.21 +/- 0.10 and the gray value was 136.82 +/- 47.42 in the model group, which were obviously lower than 0.47 +/- 0.09 and 281.44 +/- 57.98 in the normal group (both P < 0.01). However, levels of SIR1 in the acupuncture group, they were 0.32 +/- 0.11 and 199.52 +/- 58.12, which were significantly increased compared with those in the model group (both P < 0.05).
CONCLUSION:
The reinforcing-kidney and regulating-Governor Vessel method of acupuncture and moxibustion for AD could improve ultrastructure of mitochondria and increase levels of SIR1 to achieve the aim of recovering injury of mitochondria and protecting function of mitochondria.
PMID: 24796053 [PubMed - in process]




BMC Complement Altern Med. 2014 May 31;14(1):178. [Epub ahead of print]
Brain areas involved in the acupuncture treatment of AD model rats: a PET study.
Lu Y, Huang Y, Tang C, Shan B, Cui S, Yang J, Chen J, Lin R, Xiao H, Qu S, Lai X.
Abstract
BACKGROUND:
Acupuncture may effectively treat certain symptoms of Alzheimer's disease (AD). Although several studies have used functional brain imaging to investigate the mechanisms of acupuncture treatment on AD, these mechanisms are still poorly understood. We therefore further explored the mechanism by which needling at ST36 may have a therapeutic effect in a rat AD model.
METHODS:
A total of 80 healthy Wistar rats were divided into healthy control (n = 15) and pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model rats were randomly divided into three groups: the model group (n = 15), the sham-point group (n = 15), and the ST36 group (n = 15). The above three groups underwent PET scanning. PET images were processed with SPM2.
RESULTS:
The brain areas that were activated in the sham-point group relative to the model group were primarily centred on the bilateral limbic system, the right frontal lobe, and the striatum, whereas the activated areas in the ST36 group were primarily centred on the bilateral limbic system (pyriform cortex), the bilateral temporal lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared with the sham-point group, the ST36 group showed greater activation in the bilateral amygdalae and the left temporal lobe.
CONCLUSION:
We concluded that needling at a sham point or ST36 can increase blood perfusion and glycol metabolism in certain brain areas, and thus may have a positive influence on the cognition of AD patients.




Zhen Ci Yan Jiu. 2014 Apr;39(2):142-7.
[Effect of electroacupuncture intervention at different time-points of post-modeling on hippocampal monoamine neurotransmitter levels in mice with vascular dementia].
[Article in Chinese]
Zhang HZ, Liang YL, Zhang XJ, Zhang C, Sun YH, Zhang XJ, Xu XK, Jia RG, Wang XG.
Abstract
OBJECTIVE:
To observe the effect of electrocupuncture (EA) intervention at different time-points of post-modeling on behavior and hippocampal monoamine neurotransmitter noradrenalin (NE), dopamine (DA) and 5-hydroxytrypamine (5-HT) contents in vascular dementia (VD) mice, so as to study its mechanism underlying improvement of VD.
METHODS:
A total of 60 Kunming mice were randomized into sham-operation control (n = 20), VD model (n = 20), EA-day (D)-1 (EA treatment was given from the 1st day on after modeling, n = 10), EA-D-3 (EA was given from the 3rd day on after modeling, n = 10) groups. VD model was established by occlusion of the bilateral cervical common arteries and reperfusion. EA (2 Hz/80 Hz) was applied to "Baihui" (GV 20), "Dazhui" (GV 14),"Zusanli" (ST 36) and "Geshu"(BL 17) for 10 min, once daily for 15 days. Hippocampal NE, DA and 5-HT contents were assayed by fluorospectrophotometry. The mouse's learning-memory ability was assessed by step-down tests.
RESULTS:
In comparison with the sham-operation control group, the learning-memory ability (marked increase of reaction time and error times, decrease of step-down latency) was apparently lowered in the model group (P < 0.01). The hippocampal NE, DA and 5-HT contents were significantly lower in the model group than in the sham-operation group (P < 0.01). Compared with the model group, the mice's learning-memory ability (marked decrease of reaction time and error times, increase of step-down latency) was significantly increased in EA intervention groups (P < 0.01), and hippocampal NE, DA and 5-HT levels were significantly increased (P < 0.01), and the effect of EA-D-3 group was obviously better than that of the EA-D-1 group (P < 0.05, P < 0.01).
CONCLUSION:
EA can improve the VD mice's learning-memory ability, which is closely related to its effects in up-regulating hippocampal NE, DA and 5-HT contents, and the effect of later EA intervention after modeling is better.




Neural Regen Res. 2014 May 1;9(9):968-72. doi: 10.4103/1673-5374.133148.
Acupuncture and moxibustion reduces neuronal edema in Alzheimer's disease rats.
Zhou H, Sun G, Kong L, Du Y, Shen F, Wang S, Chen B, Zeng X.
Author information


Abstract
To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer's disease, we established a rat model of Alzheimer's disease and measured axin and β-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacupuncture, or both, at Baihui (GV20) and Shenshu (BL23). Axin expression was lower, β-catenin expression was greater, and neuronal cytoplasmic edema was visibly prevented in the rats that had received the pretreatments. Our results suggest that the mechanism underlying the neuroprotective effect of acupuncture and moxibustion in Alzheimer's disease is associated with axin and β-catenin expression in the Wnt signal transduction pathway.




Zhen Ci Yan Jiu. 2014 Aug;39(4):272-7.
[Effect of electroacupuncture intervention on autophagy pathway in APP 695 V 717 I transgenic mice].
[Article in Chinese]
Xue WG, Zhang Z, Xu H, Ge GL, Bai LM.
Abstract
OBJECTIVE:
To observe the effect of electroacupuncture (EA) therapy on the intraneuronal Abeta1-42 and dysfunction of autophagy pathway, so as to reveal its mechanism underlying improvement of Alzheimer's disease (AD).
METHODS:
APP 695 V 717 I transgenic female mice were randomly divided into model group (n = 6) and EA group (n = 6); and C 57 BL/6 mice were used as the control group (n = 6). After 3 months' treatment by EA therapy at "Baihui" (GV 20) and "Yongquan" (KI 1) (15 min, once every other day, 2 Hz/100 Hz, 1-2 mA), the expression level of Abeta1-42 of the striate cortex was detected by immunohistochemistry. TUNEL staining was used to detect the degree of apoptosis of the striate cortex, and ultrastructural changes of autophagosome in the cortex were observed using electron microscope.
RESULTS:
In comparison with the control group, Abeta1-42 expression level and the apoptotic neurons in the striate cortex were significantly up-regulated in the model group (P < 0.01). Following EA intervention for 3 months, the Abeta1-42 expression level and the number of apoptotic neurons were significantly decreased in the EA group (P < 0.01, P < 0.05). Accordingly, transgenic induced dark degenerated neurons exhibiting irregular body deformation, analosis, and abundant secondary lysosomes and autophagosomes were reduced in the EA group.
CONCLUSION:
EA intervention can effectively down-regulate Abeta1-42 expression and number of the apoptotic neurons in the striate cortex in APP transgenic model mice, which may contribute to its effect in improving pathological changes of ultrastructure of neurons.




Neural Regen Res. 2014 Jun 1;9(11):1163-8. doi: 10.4103/1673-5374.135319.
Acupuncture at the Taixi (KI3) acupoint activates cerebral neurons in elderly patients with mild cognitive impairment.
Chen S1, Xu M2, Li H3, Liang J4, Yin L2, Liu X4, Jia X5, Zhu F5, Wang D5, Shi X4, Zhao L6.
Author information


Abstract
Our previous findings have demonstrated that acupuncture at the Taixi (KI3) acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed significantly between elderly patients with mild cognitive impairment and healthy elderly controls. Results showed that 20 brain regions were activated in both groups of participants, including the bilateral anterior cingulate gyrus (Brodmann areas [BA] 32, 24), left medial frontal cortex (BA 9, 10, 11), left cuneus (BA 19), left middle frontal gyrus (BA 11), left lingual gyrus (BA 18), right medial frontal gyrus (BA 11), bilateral inferior frontal gyrus (BA 47), left superior frontal gyrus (BA11), right cuneus (BA 19, 18), right superior temporal gyrus (BA 38), left subcallosal gyrus (BA 47), bilateral precuneus (BA 19), right medial frontal gyrus (BA 10), right superior frontal (BA 11), left cingulate gyrus (BA 32), left precentral gyrus (BA 6), and right fusiform gyrus (BA 19). These results suggest that acupuncture at the Taixi acupoint in elderly patients with mild cognitive impairment can also activate some brain regions.



J Vet Med Sci. 2014 Oct 22. [Epub ahead of print]
Electroacupuncture at the Zusanli and Baihui acupoints ameliorates type-2 diabetes-induced reductions in proliferating cells and differentiated neuroblast in the hippocampal dentate gyrus with increasing brain-derived neurotrophic factor levels.
Chung JY1, Yoo DY, Im W, Choi JH, Yi SS, Youn HY, Hwang IK, Seong JK, Yoon YS.
Author information


Abstract
In the current study, we investigated whether electroacupuncture (EA) can inhibit pathological reductions in neurogenesis. Zucker diabetic fatty (ZDF) rats at 7 weeks of age were anesthetized with zoletil, and sham-acupuncture or EA at the Zusanli (ST36) and Baihui (GV20) acupoints was administered once a day for 5 weeks. In the ZDF group that received sham-EA (ZDF-Sham group), the blood glucose level was significantly increased together with age as compared to the control littermates (Zucker lean control [ZLC] rat). In contrast, proliferating cells and differentiated neuroblasts were significantly decreased in the ZDF-Sham group compared to the ZLC group. Although EA treatment decreased blood glucose levels, this was not statistically significant when compared to blood glucose levels changes in the ZDF-Sham group. However, proliferating cells and differentiated neuroblasts were significantly increased with EA in ZDF rats as compared to those in the ZDF-Sham group. Brain-derived neurotrophic factor (BDNF) levels were significantly decreased in hippocampal homogenates of ZDF-Sham group compared to those in the ZLC group. The EA treatment significantly increased the BDNF levels compared to those in the ZDF-Sham group, and BDNF levels in this group were similar to those in the ZLC group. These results suggest that EA at ST36 and GV20 can ameliorate the reductions in proliferating cells and differentiated neuroblasts in the dentate gyrus induced by type-2 diabetes without significantly reducing blood glucose levels with increasing BDNF levels.



PLoS One. 2014 Nov 26;9(11):e113126. doi: 10.1371/journal.pone.0113126. eCollection 2014.
EGb761 Provides a Protective Effect against Aβ1-42 Oligomer-Induced Cell Damage and Blood-Brain Barrier Disruption in an In Vitro bEnd.3 Endothelial Model.
Wan WB1, Cao L2, Liu LM3, Kalionis B4, Chen C5, Tai XT6, Li YM3, Xia SJ7.
Author information


Abstract
Alzheimer's disease (AD) is the most common form of senile dementia which is characterized by abnormal amyloid beta (Aβ) accumulation and deposition in brain parenchyma and cerebral capillaries, and leads to blood-brain barrier (BBB) disruption. Despite great progress in understanding the etiology of AD, the underlying pathogenic mechanism of BBB damage is still unclear, and no effective treatment has been devised. The standard Ginkgo biloba extract EGb761 has been widely used as a potential cognitive enhancer for the treatment of AD. However, the cellular mechanism underlying the effect remain to be clarified. In this study, we employed an immortalized endothelial cell line (bEnd.3) and incubation of Aβ1-42 oligomer, to mimic a monolayer BBB model under conditions found in the AD brain. We investigated the effect of EGb761 on BBB and found that Aβ1-42 oligomer-induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS), were attenuated by treatment with EGb761. Moreover, treatment of the cells with EGb761 decreased BBB permeability and increased tight junction scaffold protein levels including ZO-1, Claudin-5 and Occludin. We also found that the Aβ1-42 oligomer-induced upregulation of the receptor for advanced glycation end-products (RAGE), which mediates Aβ cytotoxicity and plays an essential role in AD progression, was significantly decreased by treatment with EGb761. To our knowledge, we provide the first direct in vitro evidence of an effect of EGb761 on the brain endothelium exposed to Aβ1-42 oligomer, and on the expression of tight junction (TJ) scaffold proteins and RAGE. Our results provide a new insight into a possible mechanism of action of EGb761. This study provides a rational basis for the therapeutic application of EGb761 in the treatment of AD.



Physiol Behav. 2014 Dec 3. pii: S0031-9384(14)00603-9. doi: 10.1016/j.physbeh.2014.12.001. [Epub ahead of print]
Hippocampal cAMP/PKA/CREB is Required for Neuroprotective Effect of Acupuncture.
Li QQ1, Shi GX1, Yang JW1, Li ZX1, Zhang ZH1, He T1, Wang J1, Liu LY1, Liu CZ2.
Author information


Abstract
Acupuncture has beneficial effects in vascular dementia (VaD) patients. The underlying mechanism, however, remains unknown. The present study was designed to investigate whether the cAMP/PKA/CREB cascade is involved in the mechanism of acupuncture in cerebral multi-infarction rats. In this study, cerebral multi-infarction was modeled in adult Wistar rats by homologous blood clot emboli. After a two-week acupuncture treatment at Zusanli (ST36), hippocampal-dependent memory was tested by employing radial arm maze test. The hippocampus was isolated for analyses of cAMP concentration, phosphodiesterase (PDE) activity and CREB/pCREB and ERK/pERK expressions. The Morris water maze (MWM) task and CREB phosphorylation were evaluated in the presence of PKA-selective peptide inhibitor (H89). The radial arm maze test results demonstrated that acupuncture treatment at ST36 reversed hippocampal-dependent memory in impaired animals. Compared to those of the impaired group, cAMP concentration, PKA activity and pCREB and pERK expressions were increased following acupuncture therapy. Finally, the blockade of PKA reversed the increase in CREB phosphorylation and the improvement in recognitive function induced by acupuncture treatment. These results suggests that acupuncture could improve hippocampus function by modulating the cAMP/PKA/CREB signaling pathway, which represents a molecular mechanism of acupuncture for recognitive function in cerebral multi-infarction rats.



Zhen Ci Yan Jiu. 2014 Dec;39(6):431-6.
[Effect of electroacupuncture pretreatment on apoptotic neurons and expression of GRP 78 and GADD 153 in the hippocampus in rats with global cerebral ischemia/reperfusion injury].
[Article in Chinese]
Chen HL, Qi H, Liu XJ, Wang MS.
Abstract
OBJECTIVE:
To observe the effect of electroacupuncture (EA) pretreatment on the number of survival neurons and the expression of glucose regulated protein 78 (GRP 78) and growth arrest and DNA damage-inducible gene 153 (GADD 153) in the hippocampus in rats with global cerebral ischemia /reperfusion injury (CI/R), so as to study its underlying mechanism in neuroprotective action.
METHODS:
SD male rats were randomly divided into 3 groups (n =48 each):sham operation,Cl/R model and EA pretreatment group. Global CI/R model was induced by 4-vessel occlusion (bilateral vertebral artery cauterization and bilateral carotid artery ligation for 5 min, followed by reperfusion). Before modeling, EA pretreatment of "Baihui" (GV 20) and "Dazhui" (GV 14, 2 Hz/15 Hz, 1 mA) was given to rats of the EA pretreatment group for 30 min, once daily for 5 days. At 6, 12, 24 and 48 h after CI/R, the hippocampus tissues of rats in different subgroups were separately sampled to be stained with H. E. method for detecting the number of the survived neurons, stained with TUNEL method for assaying the apoptotic neurons in the CA 1 region, and processed with Western blot (WB) for assaying the expression of GRP 78 and GADD 153 proteins.
RESULTS:
Compared with the sham group, the number of hippocampal survival neurons was significantly decreased at the time-points of 12 h, 24 h and 48 h after CI/R in the model group (P<0. 05) and was apparently increased by EA pretreatment at 24 h and 48 h (P<0. 05). The number of the apoptotic neurons in the hippocampal CA 1 region at the time-points of 6 h, 12 h, 24 h and 48 h after CI/R was significantly bigger in the model group than in the sham group (P<0. 05), and was obviously decreased at 12 h, 24 h, 48 h after CI/R in the EA pretreatment group (P<0.05). WB detection showed that the expression levels of hippocampal GRP 78 and GADD 153 proteins at the four time-points after CI/R were significantly higher in the model group than in the sham group (P<0. 05). Compared with the model group, hippocampal GRP 78 protein expression levels at the 4 time-points were further markedly up-regulated (P<0.05), while GADD 153 protein expression levels at the 4 time-points were significantly suppressed in the EA pretreatment group (P<0.05).
CONCLUSION:
EA pretreatment can effectively suppress the number of hippocampal apoptotic neurons and increase survival rate of neurons in CI/R rats, which may be closely associated with its effects in up-regulating the expression of GRP 78 protein and down-regulating the expression of GADD 153 protein in the hippocampus.


Evid Based Complement Alternat Med. 2015;2015:393569. doi: 10.1155/2015/393569. Epub 2015 Feb 25.
Electroacupuncture Suppressed Neuronal Apoptosis and Improved Cognitive Impairment in the AD Model Rats Possibly via Downregulation of Notch Signaling Pathway.
Guo HD1, Tian JX1, Zhu J1, Li L2, Sun K3, Shao SJ1, Cui GH4.
Author information


Abstract
Acupuncture is a potential strategy for the treatment of Alzheimer's disease (AD) and the possible mechanisms worth to be explored. In this study, we proposed and tested the hypothesis that whether Notch signaling pathway is involved in the effect of electroacupuncture (EA) treatment. Rats that received EA treatment on the acupoints of Baihui (Du 20) and Shenshu (BL 23) had shorter latency and remained in the original platform quadrant longer and crossed the former platform contained quadrant more frequently compared to the Aβ injection rats without EA treatment. EA obviously alleviated the cell apoptosis resulted by Aβ infusion in hippocampus CA1 regions through upregulating the expression of Bcl-2 and downregulating the expression of Bax. EA could further obviously promote the expression of synapsin-1 and synaptophysin in hippocampus. Aβ injection significantly increased the expression of Notch1, Jag1, and Hes1 mRNA, while EA treatment downregulated the level of Notch1 and Hes1 mRNA in hippocampus, but not Jag1 mRNA. Our data suggested that EA treatment improved learning and memory function in the AD rat model partially through downregulating Notch signaling pathway.


Zhen Ci Yan Jiu. 2015 Feb;40(1):6-12.
[Effects of scalp-acupuncture on astrocyte apoptosis in hippocampal CA 1 region in rats with vascular dementia].
[Article in Chinese]
Tian WJ, Huang LN, Wang RH, An JM, Zhang M.
Abstract
OBJECTIVE:
To observe the effect of scalp-acupuncture intervention on the expression of Bcl-2 of astrocytes in the hippocampus in vascular dementia (VD) rats, so as to reveal its underlying mechanism in improving VD.
METHODS:
A total of 40 male SD rats were randomly divided into normal control, sham-operation, VD model, and scalp-acupuncture groups (n=10 in each group). The VD model was established by using modified Pulsinelli 4-vessel-occlusion method. Scalp-acupuncture was applied to bilateral "Daozang Shangjiao" and bilateral "Jiyi", and "Siwei" acupoints according to FANG's scalp-acupuncture therapy for 30 min, once daily for 10 days. The rat's learning-memory ability was detected by Morris water maze tests, and the expression of apoptosis related proteins Bcl-2 of astrocytes in the hippocampus was detected by immunofluorescence double labeling technique and Western blot, respectively.
RESULTS:
Morris water maze tests showed that the average escape latency of place navigation test and the duration of the first platform-site crossover (space probing test) were significantly increased in the model group compared with the normal control group (P<0.01), and the number of platform-site crossovers in 2 min was markedly decreased in the model group (P<0.01). The increased average escape latency and the increased duration of first platform-site crossover were markedly shortened in the scalp-acupuncture group in comparison with the model group (P<0.01), and the number of the platform crossovers in 2 min was significantly increased in the scalp-acupuncture group (P<0.01). The expression of Bcl-2 protein and the number of GFAP/Bcl-2-labeled cells of hippocampal CA 1 region in the model group were remarkably decreased compared with the normal control group (P<0.01). After scalp-acupuncture intervention, the decreased Bcl-2 protein expression level and the number of double-labeled GFAP/Bcl-2 cells were significantly up-regulated in the scalp-acupuncture group compared with the model group (P<0.01). No significant differences were found between the normal control and sham-operation groups in the escape latency, duration of the first platform-site crossover, number of platform crossovers in 2 min, number of GFAP/Bcl-2 double labeled cells and the expression level of hippocampal Bcl-2 protein (P>0.05).
CONCLUSION:
Scalp-acupuncture can effectively regulate the expression of apoptosis related proteins Bcl-2 of astrocytes in the CA 1 region of hippocampus in rats with VD, which may contribute to its effect in the improvement of VD.



2014 Dec;29(8):739-48. doi: 10.1177/1533317514536600. Epub 2014 Jun 6.
Acupuncture stimulation of Taichong (Liv3) and Hegu (LI4) modulates the default mode network activity in Alzheimer's disease.
Liang P1, Wang Z2, Qian T3, Li K4.
Author information


Abstract
OBJECTIVES:
The acupuncture has been used in the therapy of Alzheimer disease (AD), however, its neural underpins are still unclear. The aim of this study is to examine the acupuncture effect on the default mode network (DMN) in AD by using resting state functional magnetic resonance imaging (RS-fMRI).
METHODS:
Twenty-eight subjects (14 AD and 14 normal controls (NC)) participated in this study. RS-fMRI data were acquired before and after acupuncture, while during the acupuncture, the procession of acupuncture stimulation on the acupoints of Tai chong (Liv3) and Hegu (LI4) lasted for 3 minutes.
RESULTS:
Region of interest analysis showed that the impaired DMN connectivity in AD (identified by comparing the pre-acupuncture RS-fMRI of AD and NC), specifically the left cingulate gyrus (CG) and right inferior parietal lobule (IPL), were significantly changed for the better. The whole-brain exploratory analysis further demonstrated these results and found some new regions respond to the acupuncture effect on AD, with a cluster in the left posterior cingulate cortex (PCC), the right middle temporal gyrus (MTG) together with right IPL showed increased within-DMN connectivity; and the bilateral CG and left PCu showed decreased within-DMN connectivity. Moreover, the acupuncture effect on the right MTG was significantly correlated with disease severity as measured by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores.
CONCLUSION:
It was found that the acupuncture stimulation could modulate the DMN activity in AD. The current findings suggest that the acupuncture treatment on the relative earlier AD patients might have a better therapy effect.


BMC Complement Altern Med. 2015 Apr 28;15(1):133. [Epub ahead of print]
Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.
Li F1,2, Yan CQ3,4, Lin LT5,6, Li H7,8, Zeng XH9,10, Liu Y11,12, Du SQ13, Zhu W14, Liu CZ15.
Author information


Abstract
BACKGROUND:
Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity.
METHODS:
Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells.
RESULTS:
We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P < 0.05) and tended to decrease the number of astrocytes (P = 0.063). However, there was no significant change in the synaptic bouton number of hippocampal CA1 area in any of the groups (P > 0.05).
CONCLUSIONS:
These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.


Medicine (Baltimore). 2015 Jun;94(22):e933.
The Effectiveness and Safety of Acupuncture for Patients With Alzheimer Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Zhou J1, Peng W, Xu M, Li W, Liu Z.
Author information


Abstract
The use of acupuncture for treating Alzheimer disease (AD) has been increasing in frequency over recent years. As more studies are conducted on the use of acupuncture for treating AD, it is necessary to re-assess the effectiveness and safety of this practice.The objective of this study was to assess the effectiveness and safety of acupuncture for treating AD.Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, Embase, PsycINFO, Chinese Biomedicine Literature (CBM), Chinese Medical Current Content (CMCC) and China National Knowledge Infrastructure (CNKI) were searched from their inception to June 2014.Randomized controlled trials (RCTs) with AD treated by acupuncture or by acupuncture combined with 1 kind of drugs were included.Two authors extracted data independently. The continuous data were expressed as mean differences (MD) with 95% confidence intervals (CIs). Weighted MD (WMD) was used instead of standardized MD (SMD) when the same scales were used. Adverse reactions related to acupuncture were also investigated.Ten randomized controlled trials with a total of 585 participants were included in the meta-analysis. The combined results of 6 trials showed that acupuncture was better than drugs at improving scores on the Mini Mental State Examination (MMSE) scale (MD 1.05, 95% CI 0.16-1.93). Evidence from the pooled results of 3 trials showed that acupuncture plus donepezil was more effective than donepezil alone at improving the MMSE scale score (MD 2.37, 95% CI 1.53-3.21). Out of 141 clinical trials, 2 trials reported the incidence of adverse reactions related to acupuncture. Seven out of 3416 patients had adverse reactions related to acupuncture during or after treatment; the reactions were described as tolerable and not severe.Acupuncture may be more effective than drugs and may enhance the effect of drugs for treating AD in terms of improving cognitive function. Acupuncture may also be more effective than drugs at improving AD patients' ability to carry out their daily lives. Moreover, acupuncture is safe for treating people with AD.Protocol registration: PROSPERO CRD42014009619.Protocol published in BMJ-open.



Evid Based Complement Alternat Med. 2015;2015:310591. doi: 10.1155/2015/310591. Epub 2015 Jul 30.
Discovery of Acupoints and Combinations with Potential to Treat Vascular Dementia: A Data Mining Analysis.
Feng S1, Ren Y1, Fan S2, Wang M1, Sun T1, Zeng F1, Li P2, Liang F1.
Author information


Abstract
The prevalence of vascular dementia (VaD) is high among the elderly. Acupuncture, a popular therapeutic method in China, can improve memory, orientation, calculation, and self-managing ability in VaD patients. However, in clinical acupuncture and acupuncture research, the selection of acupoints to treat VaD remains challenging. This study aimed to discover acupoints and acupoint combinations with potential for VaD based on data mining. After database searching and screening for articles on clinical trials evaluating the effects of acupuncture on VaD, 238 acupuncture prescriptions were included for further analysis. Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Shuigou (GV 26), and Shenting (GV 24) appeared most frequently in the modern literature and are potential acupoints for VaD. Combinations between Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Shenting (GV 24), Shuigou (GV 26), and Zusanli (ST 36) were most frequent and represent potential combinations for VaD treatment. These results provide a reference for the selection and combination of acupoints to treat VaD in clinical acupuncture and acupuncture research.
Am J Alzheimers Dis Other Demen.



Acupunct Med. 2015 Dec 9. pii: acupmed-2015-010865. doi: 10.1136/acupmed-2015-010865. [Epub ahead of print]
Effects of acupuncture at HT7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-FDG-PET study.
Lai X1, Ren J2, Lu Y3, Cui S4, Chen J5, Huang Y2, Tang C1, Shan B6, Nie B6.
Author information


Abstract
OBJECTIVE:
To explore the effects of acupuncture at HT7 on different cerebral regions in a rat model of Alzheimer's disease (AD) with the application of 18F-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET).
METHODS:
Sixty Wistar rats were included after undergoing a Y-maze electric sensitivity test. Ten rats were used as a healthy control group. The remaining 50 rats were injected stereotaxically with ibotenic acid into the right nucleus basalis magnocellularis and injected intraperitoneally with D-galactose. AD was successfully modelled in 36 rats, which were randomly divided into three groups (n=12 each): the AD group, which remained untreated; the AD+HT7 group, which received 20 sessions of acupuncture at HT7 over 1 month; and the AD+Sham group, which received acupuncture at a distant non-acupuncture point. Total reaction time (TRT) was measured by Y-maze and 18F-FDG-PET scans were conducted on day 1 and 30. PET images were processed with Statistical Parametric Mapping 8.0.
RESULTS:
Pre-treatment, TRT was greater in all AD groups versus controls (mean±SD 24.10±2.48 vs 41.34±5.00 s). Post-treatment, TRT was shortened in AD+HT7 versus AD+Sham and AD groups (p<0.0001, two-way analysis of variance). Glucose metabolic activity in the hippocampus, thalamus, hypothalamus, frontal lobe, and temporal lobe was decreased in AD rats compared with healthy controls and relatively elevated after HT7 acupuncture. Compared with sham acupuncture, HT7 needling had a greater positive influence on brain glucose metabolism.
CONCLUSIONS:
Needling at HT7 can improve memory ability and cerebral glucose metabolic activity of the hippocampus, thalamus, hypothalamus, and frontal/temporal lobes in an AD rat model.

Acupunct Med. 2016 Feb 19. pii: acupmed-2015-010894. doi: 10.1136/acupmed-2015-010894. [Epub ahead of print]
Electroacupuncture improves memory and protects neurons by regulation of the autophagy pathway in a rat model of Alzheimer's disease.
Guo HD1, Zhu J1, Tian JX1, Shao SJ1, Xu YW2, Mou FF1, Han XJ1, Yu ZH3, Chen JL3, Zhang DY4, Zhang LS1, Cui GH5.
Author information


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 Aβ1-40 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.
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.