Acupuncture May Be a Potential Complementary Therapy for Alzheimer's Disease: A Network Meta-Analysis.

With Alzheimer's disease (AD) becoming a worldwide problem, traditional Chinese medicine (TCM), especially acupuncture, stands out as a complementary therapy because of its feature-"treatment based on syndrome differentiation". This systematic review and network meta-analysis (NMA) confirms the complement effect of acupuncture and explores the best combination of therapy for AD based on the total effect and activity of daily living scale (ADL). We searched relevant randomized controlled trials (RCTs) that applied acupuncture for treating AD. 58 studies with 4334 patients were included in accordance with PRISMA guidelines. The results showed that for the total effect, the order of probability for the effect: acupuncture + western medicine > acupuncture + herbal medicine > acupuncture > acupuncture + western medicine + herbal medicine. For the ADL score, the order of probability for the effect: acupuncture + western medicine > acupuncture > acupuncture + western medicine + herbal medicine > acupuncture + herbal medicine. The combination of acupuncture and medicine has a better clinical effect than acupuncture only in a way. Acupuncture + western medicine has an obvious and exact improvement in the curative effect from both total effect and ADL score, but further higher quality studies, which can detail the classification of these interventions, are still needed to verify it.

Effects and safety of acne vulgaris with external application of herbal medicines: A protocol for systematic review and meta analysis.

BACKGROUND: Acne vulgaris (AV) is a common dermatologic disease. The morbidity is increasing annually. External application of herbal medicines (EAHM) has been pervasively used in the therapy of AV. EAHM , as the traditional Chinese therapy, is widely applied in clinical trials for AV. The aim of this review is to systematically evaluate the efficacy and safety of EAHM in the therapy for AV. METHODS: We will conduct an electronic search of 13 databases from their inception to May, 2020, including PubMed, EMBASE, MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform, Wanfang China database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, as well as China's Conference Papers Database and China Dissertation database. Other valid search strategies will also be retrieved to complete this review. All randomized controlled trials in which EAHM was used for the treatment of AV will be adopted. Two researchers will select eligible studies respectively according to a predefined protocol. Methodological quality will be assessed with Cochrane risk of bias by means of RevMan V.5.3.5 software. RESULTS: This systematic view will present a high-quality synthesis based on current evidence of EAHM intervention for AV patients. CONCLUSION: The summary of our systematic view will provide evidence to judge whether EAHM is an effective and safe intervention for AV patients.

Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3ß Signaling Pathway in Alzheimer's Disease Model Mice.

BACKGROUND: Alzheimer's disease (AD) is mainly manifested as a continuous and progressive decline in cognitive ability. Neurofibrillary tangles (NFTs) are pathological hallmarks of AD and due to accumulated phosphorylated Tau. Glycogen synthase kinase-3ß (GSK3ß), as a major Tau kinase and a downstream target of the serine protein kinase B (AKT) signaling pathway, can regulate Tau phosphorylation in AD. Importantly, the AKT/GSK3ß signaling pathway is involved in glucose metabolism, and abnormal glucose metabolism is found in the AD brain. Numerous studies have shown that electroacupuncture (EA), which is thought to be a potential complementary therapeutic approach for AD, can protect cognitive ability to a certain extent. OBJECTIVE: The purpose of this experiment was to investigate whether the protective and beneficial mechanism of EA on cognition was mediated by the AKT/GSK3ß signaling pathway, thereby improving glucose metabolism and Tau phosphorylation in the brain. METHODS: EA was applied to the Baihui (GV20) and Yintang (GV29) acupoints of 6-month-old amyloid precursor protein (APP)/presenilin-1 (PS1) mice for 20 min, and then quickly prick Shuigou (GV26) acupoint. The intervention was performed once every other day for 28 days. The Morris water maze (MWM) test was performed on C57BL/6N (Non-Tg) mice, APP/PS1 (Tg) mice and EA-treated Tg (Tg + EA) mice to evaluate the effect of EA therapy on cognitive function. 18F-FDG positron emission tomography (PET), immunohistochemistry, and western blotting (WB) were used to investigate the possible mechanism underlying the effect of EA on AD. RESULTS: EA treatment significantly improved the cognition of APP/PS1 mice and the glucose uptake rate in the hippocampus. Furthermore, EA inhibited the phosphorylation of Tau (Ser199 and Ser202) proteins by inducing AKT (Ser473) and GSK3ß (Ser9) phosphorylation. CONCLUSION: These results demonstrate that EA intervention protects cognition by enhancing glucose metabolism and inhibiting abnormal phosphorylation of Tau protein in the AD model mice, and the AKT/GSK3ß pathway might play an irreplaceable role in the regulation process.

Electroacupuncture Enhances Cognition by Promoting Brain Glucose Metabolism and Inhibiting Inflammation in the APP/PS1 Mouse Model of Alzheimer's Disease: A Pilot Study.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease, yet there is no effective treatment. Electroacupuncture (EA) is a complementary alternative medicine approach. In clinical and animal studies, EA promotes cognition in AD and vascular dementia. It has been previously reported that cognitive decline in AD might be closely related to reduced glucose intake in the brain. It is worth mentioning that the regions of glucose hypometabolism are usually found to be associated with neuroinflammation. OBJECTIVE: This study is to explore whether the protective mechanism of EA on cognition is related to the regulation of glucose metabolism and neuroinflammation. METHODS: APP/PS1 mice were randomly divided into AD group and the treatment (AD + EA) group. In the AD + EA group, EA was applied on Baihui (GV20) and Yintang (GV29) for 20 min and then pricked at Shuigou (GV26), once every alternate day for 4 weeks. Morris water maze (MWM) tests were performed to evaluate the effects of EA treatment on cognitive functions. 18F-FDG PET, immunofluorescence, and western blot were used to examine the mechanisms underlying EA effects. RESULTS: From MWM tests, EA treatment significantly improved cognition of APP/PS1 mice. From the 18F-FDG PET, the levels of uptake rate of glucose in frontal lobe were higher than the AD group after EA. From immunofluorescence and western blot, amyloid-ß (Aß) and neuroinflammation were reduced after EA. CONCLUSION: These results suggest that EA may prevent cognitive decline in AD mouse models by enhancing glucose metabolism and inhibiting inflammation-mediated Aß deposition in the frontal lobe.

Electroacupuncture Ameliorates Cognitive Impairment by Inhibiting the JNK Signaling Pathway in a Mouse Model of Alzheimer's Disease.

Electroacupuncture (EA) has become popular for its adjustable strength and frequency and easy quantification in the clinic and has demonstrated therapeutic potential for Alzheimer's disease (AD). However, the mechanism remains unknown. Abnormally activated c-Jun N-terminal kinase (JNK) has been closely related to the pathological process of AD. The aim of this study was to investigate the effect of EA on cognitive impairment and the role of the JNK signaling pathway in AD model amyloid precursor protein (APP)/presenilin 1 (PS1) mice. The memory and learning ability of each group was assessed using the Morris Water Maze (MWM). Immunofluorescence, immunohistochemistry and Western blot were performed to measure the expression of APP, JNK, phosphorylated (P-)JNK, mitogen-activated protein kinase 4 (MKK4), MKK7, c-Jun and caspase-3 in hippocampal tissue samples in APP/PS1 mice after EA intervention. Obvious cognitive deficits were observed in the AD model APP/PS1 mice in the MWM test and were associated with JNK signaling pathway activation and APP upregulation. Four weeks of EA significantly ameliorated the cognitive impairments and inhibited JNK signaling pathway activation and APP upregulation. Taken together, the findings demonstrated that EA can reverse cognitive deficits and substantially lower the burden of APP in AD model APP/PS1 mice, at least partially through inhibiting the JNK signaling pathway and regulating apoptosis signals. Therefore, EA may offer an effective alternative therapeutic approach for AD.

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study.

BACKGROUND AND OBJECTIVE: Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. METHODS: Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. RESULTS: The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration-time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. CONCLUSION: Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood-brain barrier during cerebral ischemia-reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.

Jiedu Sangen Decoction Reverses Epithelial-to-mesenchymal Transition and Inhibits Invasion and Metastasis of Colon Cancer via AKT/GSK-3ß Signaling Pathway.

Ethnopharmacology relevance: Jiedu Sangen Decoction (JSD), an empirical prescription of Traditional Chinese Medicine (TCM), has been reported to inhibit invasion and metastasis of colon cancer in our previous study. The aim of this study was to investigate the mechanism of JSD-triggered inhibition of invasion and metastasis in colon cancer. Methods: In vitro, AKT1 knockdown (si-AKT1) or overexpression (oe-AKT1) cells were successfully constructed both in SW480 and SW620 cell lines. Si-AKT1 and oe-AKT1 cells were then treated with or without JSD. Cell invasion, metastasis potential and expression of epithelial-mesenchymal transformation (EMT)-related and AKT1/GSK-3ß proteins were then observed by wound healing, transwell, and western blot assays. In vivo, liver metastasis model mice were developed by inoculating SW480 cells. After JSD diet intervention, living fluorescence imaging and weight measurements were carried out to investigate JSD induced inhibition effects on liver metastasis of colon cancer. Immunohistochemistry and western blot assays were performed to observe tissue features and detect protein expression. Results: Invasion and metastasis potential, as well as EMT of colon cancer, can be markedly inhibited by JSD treatment or AKT1 knockdown, while enhanced by AKT1 overexpression. JSD-induced inhibition effects were significantly weakened when AKT1 was knocked down, while clearly enhanced when AKT1 was overexpressed. Additionally, JSD could lead to an increase in expression of E-cadherin, and a decrease in expression of N-cadherin, Vimentin, p-AKT1, AKT1, p- GSK-3ß, Snail, Slug, and Twist in colon cancer cells. Conclusion: JSD reverses EMT and inhibits invasion and metastasis of colon cancer through the AKT/GSK-3ß signaling pathway.

The effects of acupuncture on cognitive impairment of vascular dementia patients: Protocol for a systematic review and meta-analysis.

BACKGROUND: Vascular dementia (VaD) is the second prevalent dementia worldwide attributable to cognitive impairments. Acupuncture has been applied in clinic as a therapeutic modality to treat VaD. This systematic review and meta-analysis aims to evaluate current evidence to explore the effectiveness and safety of acupuncture treatment to cognitive impairment of VaD. METHODS: Randomized controlled trials will be searched restricted to their inception from January 1, 2000 to September 15, 2019. The following literature databases will be searched, including 4 English databases: PubMed, Excerpta Medica Database, the Cochrane Library, Medline, and 4 Chinese databases, namely the China National Knowledge Infrastructure Database, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical Literature Database. After the selection and extraction of eligible studies, a meta-analysis will be undertaken to assess the efficacy and safety of acupuncture on VaD. The Review Manager Software V.5.3.5 will be employed for meta-analysis to assess the risk of bias, data synthesis, and subgroup analysis. RESULTS: The systematic review and meta-analysis will be carried out to evaluate the efficacy and safety of acupuncture in the treatment of VaD, further provide an evidence-based synthesis for clinical and research applications. CONCLUSIONS: The summary of our systematic review will determine whether acupuncture intervention to VaD is safe and well-tolerated in global status.

Effects and safety of herbal medicines on patients with overactive bladder: A protocol for a systematic view and meta-analysis.

BACKGROUND: Overactive bladder (OAB) is a common disease in the urinary system. The morbidity is increasing annually. Herbal medicines have been pervasively used in the therapy of OAB. However, systematic review or meta-analysis has not been found to assess the effects and safety of herbal medicines in curing OAB at present. Hence, the systematic review is conducted to scientifically and methodically evaluate the value of its effectiveness and safety of herbal medicines on OAB. METHODS: We will collect all randomized controlled trials (RCTs) to assess the effectiveness and safety of herbal medicines on OAB. The RCTs will be searched from the electronic databases, including 7 English databases, consisting of PubMed, Excerpta Medica Database (EMBASE), MEDLINE, Web of Science, Cochrane Library, SpringerLink, and WHO International Clinical Trials Registry Platform (ICTRP), and 4 Chinese databases, namely Wanfang Chinese database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP), others valid search strategy will be adopted. All the RCTs will be assessed from the databases establishment to July 2019. We will perform the meta-analysis of RCTs when the dissertation is appropriate. We will conduct an assessment including data synthesis, bias risk, and subgroup analysis by means of Review Manager software (RevMan) V.5.3.5 software while the setting condition is met. RESULTS: This systematic view and meta-analysis will generate a summary based on the current relevant research to calculate the effects and safety of herbal medicines in promoting the therapy of OAB. Furthermore, it will provide a high-quality synthesis for participants who use herbal medicine to cure OAB. CONCLUSION: The summary of our systematic view will verify whether herbal medicines intervention could be an effective and safety approach in curing OAB.

Electroacupuncture Mitigates Hippocampal Cognitive Impairments by Reducing BACE1 Deposition and Activating PKA in APP/PS1 Double Transgenic Mice.

Increased amyloid-ß (Aß) plaque deposition is thought to be the main cause of Alzheimer's disease (AD). ß-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is the key protein involved in Aß peptide generation. Excessive expression of BACE1 might cause overproduction of neurotoxins in the central nervous system. Previous studies indicated that BACE1 initially cleaves the amyloid precursor protein (APP) and may subsequently interfere with physiological functions of proteins such as PKA, which is recognized to be closely associated with long-term potentiation (LTP) level and can effectively ameliorate cognitive impairments. Therefore, revealing the underlying mechanism of BACE1 in the pathogenesis of AD might have a significant impact on the future development of therapeutic agents targeting dementia. This study examined the effects of electroacupuncture (EA) stimulation on BACE1, APP, and p-PKA protein levels in hippocampal tissue samples. Memory and learning abilities were assessed using the Morris water maze test after EA intervention. Immunofluorescence, immunohistochemistry, and western blot were employed to assess the distribution patterns and expression levels of BACE1, APP, and p-PKA, respectively. The results showed the downregulation of BACE1 and APP and the activation of PKA by EA. In summary, EA treatment might reduce BACE1 deposition in APP/PS1 transgenic mice and regulate PKA and its associated substrates, such as LTP to change memory and learning abilities.

Manual Acupuncture Regulates Behavior and Cerebral Blood Flow in the SAMP8 Mouse Model of Alzheimer's Disease.

Background: A growing body of evidence has demonstrated that cerebrovascular function abnormality plays a key role in occurrence and worsening of Alzheimer's disease (AD). Reduction of cerebral blood flow (CBF) is a sensitive marker to early perfusion deficiencies in AD. As one of the most important therapies in complementary and alternative medicine, manual acupuncture (MA) has been used in the treatment of AD. However, the moderating effect of MA on CBF remains largely unknown. Objective: To investigate the effect of MA on the behavior and CBF of SAMP8 mice. Methods: SAMP8 mice were randomly divided into the AD, MA, and medicine (M) groups, with SAMR1 mice used as the normal control (N) group. Mice in the M group were treated with donepezil hydrochloride at 0.65 µg/g. In the MA group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 15 consecutive days. The Morris water maze and arterial spin labeling MRI were used to assess spatial learning and memory in behavior and CBF respectively. Results: Compared with the AD group, both MA and donepezil significantly decreased the escape latency (p < 0.01), while also elevating platform crossover number and the percentage of time and swimming distance in the platform quadrant (p < 0.01 or p < 0.05). The remarkable improvement in escape latency in the MA group appeared earlier than the M group, and no significant statistical significance was observed between the N and MA group with the exception of days 5 and 10. The CBF in the prefrontal lobe and hippocampus in the MA group was substantially higher than in the AD group (p < 0.05) with the exception of the right prefrontal lobe, with similar effects of donepezil. Conclusion: Manual acupuncture can effectively improve the spatial learning, relearning and memory abilities of SAMP8 mice. The increase in CBF in the prefrontal lobe and hippocampus could be an important mechanism for the beneficial cognitive effects of MA in AD.

Effects of acupuncture on patients with Alzheimer's disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the leading progressive neurodegenerative disease worldwide, accompanied with nonreversible cognitive impairments. Acupuncture, as the traditional Chinese technique, is widely applied in clinical trials for AD. The aim of this review is to evaluate the efficacy and safety of acupuncture in the aspect of antidementia. METHODS: Randomized controlled trials (RCTs) related to acupuncture treatment targeting AD will be collected. We will search the following 4 databases of electronic English resources, including PubMed, Embase, MEDLINE, Web of Science, and 4 Chinese databases, namely CNKI, CBM, VIP, and Wanfang database. All the RCTs will be searched from their inception to November 2018. After screening the studies, a meta-analysis of RCTs will be carried out. Subsequently, the assessment of bias risk, data synthesis, subgroup analysis will be conducted using RevMan V.5.3.5 software if the setting condition is met. RESULTS: This systematic view and meta-analysis will assess the efficacy and safety of acupuncture intervention on AD patients, which is fundamentally based on current published evidence, and provide a high-quality synthesis for clinical practitioners of treating AD with acupuncture, CONCLUSION:: The summary of our systematic view will determine whether acupuncture intervention could be an efficient and feasible approach to the treatment of AD patients.

Behavioral Changes and Hippocampus Glucose Metabolism in APP/PS1 Transgenic Mice via Electro-acupuncture at Governor Vessel Acupoints.

Objective: Investigating the effects of electro-acupuncture (EA) treatment on mice with Alzheimer's disease (AD), using Morris water maze (MWM) for spatial learning and memory behavior tests combined with micro-positron emission tomography (micro-PET) imaging for glucose metabolism in hippocampus. Methods: Thirty seven-month-old APP/PS1 mice were randomly divided into AD Model group (AD group), medicine group (M group) and EA group, C57BL/6 mice were used for Normal control group (N group), n = 10 in each group. Mice in M group received donepezil intervention by gavage with dose at 0.92 mg/kg. EA was applied at Baihui (GV20) and Yintang (GV29) acupoints for 20 min then pricked at Shuigou (GV26) acupoint, while mice in N, M and AD groups were received restriction for 20 min, with all treatment administrated once a day for 15 consecutive days. After the treatment, MWM was performed to observe behavioral changes in mice, then hippocampus glucose metabolism level was tested by micro-PET imaging. Results: Compared with that of AD group, the escape latency of M and EA groups declined significantly (P < 0.01), while the proportion of the platform quadrant swimming distance in total swimming distance showed an obvious increase (P < 0.01), and EA group occupied a higher percentage than that in M group. The micro-PET imaging showed that mice in AD group performed a lower glucose metabolic rate in hippocampus compared with N group (P < 0.01). Both M and EA groups presented a significant higher injected dose compared with AD group (P < 0.01), and the uptake rate of EA group was higher than M group. Conclusion: Both donepezil and EA have therapeutic effects on AD mice. To a certain extent, EA shows a better efficacy in treatment of AD by improving the spatial learning and memory ability, while also enhancing glucose metabolism in hippocampus.

The short-term effects of acupuncture on patients with diabetic gastroparesis: a randomised crossover study.

BACKGROUND: Acupuncture may improve gastrointestinal symptoms in patients with various disorders, but its efficacy in diabetic gastroparesis is unclear. OBJECTIVE: To evaluate the short-term effects of acupuncture on gastric emptying and gastroparesis symptoms in patients with diabetic gastroparesis. METHODS: In a single-blind controlled crossover trial, 25 patients with diabetic gastroparesis were randomly assigned to undergo 1 week of real acupuncture (RA) treatment followed by 1 week of sham acupuncture (SA) treatment, or vice versa, with a washout of 1 month in between. Before and after each intervention, gastric retention, the Gastroparesis Cardinal Symptom Index (GCSI), fasting blood glucose (FBG) and HbA1c levels were measured. RESULTS: 21 patients completed the study. Compared with SA treatment, RA treatment was associated with significantly greater reductions in gastric retention at 2 h (-11.1±7.0%; 95% CI -13.6% to -6.2%; p<0.01) and at 4 h (-5.0±2.8%; 95% CI -6.0% to -0.2%; p=0.04) and in GCSI score (-8.0±3.4; 95% CI -8.4 to -2.8; p<0.01). There were no significant differences in FBG and HbA1c levels between RA and SA treatments. CONCLUSIONS: In patients with diabetic gastroparesis, 1 week of short-term manual acupuncture reduces gastric retention and improves gastroparesis symptoms.

Alteration of behavioral changes and hippocampus galanin expression in chronic unpredictable mild stress-induced depression rats and effect of electroacupuncture treatment.

To explore new noninvasive treatment options for depression, this study investigated the effects of electric acupuncture (EA) for depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighteen male Sprague-Dawley rats were randomly assigned into three groups: control, model, and EA groups. Rats were treated by EA once daily for 21 days. The results showed that body weight and sucrose consumption were significantly increased in EA group than in the model group. The crossing numbers and rearing numbers in the open field test significantly decreased in the model group but not in the EA group. And EA treatments upregulated levels of hippocampus galanin (Gal) in UCMS rats back to relative normal levels. The present study suggested that EA had antidepressant effects on UCMS model rats. The potential antidepressant effect may be related to upregulating Gal expression in hippocampus.

Progress of animal research on electro-acupuncture treatment for depression(△).

This paper summarized the Chinese literatures in the previous 5 years about the pre-clinical animal researches on the application of electro-acupuncture (EA) treatment for depression, searched in China National Knowledge Infrastructure (CNKI). The efficiency of EA treatment for depression and the mechanism of it were discussed, to shed light on new ideas and new fronts for the further research on depression in clinical or pre-clinical fields.

[Effect of electroacupuncture intervention on behavioral changes and hippocampal excitatory amino acid transporter mRNA expression in depression rats].

OBJECTIVE: To observe the influence of music-electroacupuncture (EA) and pulse EA on locomotor activity and hippocampal neuron numbers and excitatory amino acid transporters (EAATs) mRNA expression in depression rats, so as to explore their mechanisms underlying improvement of depression in acupuncture clinic. METHOD: Sixty SD rats were randomly divided into blank control, depression model, medication, pulse EA and music-EA groups, with 12 rats in each group. Depression model was established by using chronic unpredictable mild stress protocols combined with solitary feeding. Rats of the medication group were treated by oral administration of fluoxetine (a standard antidepressant, 2 mg/kg). EA was applied to "Baihui" (GV 20) and "Yintang" (EX-HN 3) for 20 min, once a day for 21 days. The animals' ethological changes were detected by using field tests for recording the number of crossing squares and the number of rearing. The number of hippocampal neurons were calculated under microscope after Nissl's staining of the hippocampal tissue section. Hippocampal EAAT 1 and EAAT 2 mRNA expression levels were assayed by fluorescent quantitative real-time POR. RESULTS: In comparison with the blank control group, the numbers of crossing and rearing movements, as well as the expression levels of hippocampal EAAT 1 and EAAT 2 mRNA were significantly lower in the model group (P < 0.01), while compared with the model group, the numbers of both crossing and rearing movements of the medication, pulse EA and music-EA groups were obviously increased (P < 0.01). Correspondingly, the expression levels of hippocampal EAAT 1 and EAAT 2 mRNA were considerably upregulated in the pulse EA and music-EA groups in comparison with the model group (P < 0.01). No significant differences were found among the medication, pulse EA and music-EA groups (P > 0.05). Results of Nissl's staining displayed that in the model group, the hippocampal neurons were loose in arrangement and some of them were absent, but in the medication, pulse EA and music-EA groups, the neurons were clear in shape and lined in order. CONCLUSION: Both pulse EA and music-EA can effectively improve the locomotor activity and hippocampal neuronal structure in depression rats which may be closely associated with their effects in upregulating hippocampal EAAT 1 and EAAT 2 mRNA expression.