Therapeutic Effect Of Electroacupuncture Research Articles

Effect of electroacupuncture on metabolic alterations in the hippocampus and dorsal raphe nucleus of Wistar Kyoto rats.

Depression is underpinned by a complex pathogenesis that involves the hippocampus and dorsal raphe nucleus (DRN) of the central nervous system. Although electroacupuncture (EA) is proven to be safe and effective for alleviating depression symptoms and causes minimal side effects its underlying therapeutic mechanism remains unclear. In this study, we performed targeted metabolomics to identify metabolite alterations in the hippocampus and DRN of Wistar Kyoto (WKY) rats and elucidate the role and potential mechanism of action of EA. Our results indicated that 3 weeks of consecutive EA significantly ameliorated depression-like behavior in WKY rats. Targeted metabolomics revealed 42 differentially expressed metabolites (DEMs) in the hippocampus and 97 DEMs in the DRN between Wistar and WKY rats. In addition, we observed 19 hippocampal DEMs and 41 DRN DEMs between WKY and EA-treated rats. Subsequent pathway analyses indicated that these DEMs were primarily enriched in amino acid-related metabolic pathways. Moreover, six DEMs were found to be significantly associated with at least one depression-like behavior, indicating their involvement in the pathogenesis of depression. EA intervention modulated the levels of 1-methylhistidine, 3-methylhistidine, carnosine, and riboflavin in depressed rats. Collectively, these findings demonstrate that disturbances in cerebral metabolites, especially amino acids, may be one of the causes underlying depression in WKY rats, and the therapeutic effect of EA is potentially mediated through the modulation of the levels of these metabolites.

Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer’s disease by regulating hippocampal mitochondrial dynamics

ObjectiveStudies have shown that electroacupuncture (EA) can alleviate cognitive impairments from Alzheimer’s disease (AD) by regulating the expression of adenosine monophosphate-activated protein kinase (AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial dynamics. MethodsThe four-month-old transgenic mice with amyloid precursor protein (APP)/presenilin 1 (PS1) and AMPKα1-subunit conditional knockout (AMPKα1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition, chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 mice. ResultsBoth APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway increased pathological amyloid-β (Aβ) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway, specifically by reducing pathological Aβ deposition, normalizing energy metabolism, protecting the structure and function of mitochondria, increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout. ConclusionThe regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.Please cite this article as: Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL. Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer’s disease by regulating hippocampal mitochondrial dynamics. J Integr Med. 2024; 22(5): 588–599.

Cannabinoid type 2 receptors play a crucial role in social defeat-induced depression

BackgroundThe endocannabinoid system plays a crucial role in regulating mood, but the specific involvement of cannabinoid receptor type 2 (CB2R) in depression remains poorly understood. Similarly, the mechanisms by which electroacupuncture (EA) provides therapeutic benefits for depression are not clearly defined. This research aims to explore the function of CB2R in depression and examine if the therapeutic effects of EA are associated with the hippocampal CB2R system. MethodsMice experiencing social defeat stress (SDS) were used to model depression and anxiety behaviors. We quantified hippocampal CB2R and N-arachidonoylethanolamide (AEA) levels. The efficacy of a CB2R agonist, JWH133, in mitigating SDS-induced behaviors was evaluated. Additionally, EA's impact on CB2R and AEA was assessed, along with the influence of CB2R antagonist AM630 on EA's antidepressant effects. ResultsSDS led to depressive and anxiety-like behaviors, with corresponding decreases in hippocampal CB2R and AEA. Treatment with JWH133 ameliorated these behaviors. EA treatment resulted in increased CB2R and AEA levels, while AM630 blocked these antidepressant effects. LimitationsThe study mainly focused on the SDS model, which may not entirely reflect other depression models. Besides, further investigation is needed to understand the precise mechanisms by which CB2R and AEA contribute to EA's effects. ConclusionsThe study suggests hippocampal downregulation of CB2R and AEA contributes to depression. Upregulation of CB2R and AEA in response to EA suggests their involvement in EA's antidepressant effects. These findings provide insights into the role of the hippocampal CB2R system in depression and the potential mechanisms underlying EA's therapeutic effects.

Electroacupuncture at ST25 corrected gut microbial dysbiosis and SNpc lipid peroxidation in Parkinson's disease rats.

Parkinson's disease (PD) remains one kind of a complex, progressive neurodegenerative disease. Levodopa and dopamine agonists as widely utilized PD therapeutics have not shown significant positive long-term outcomes. Emerging evidences indicate that electroacupuncture (EA) have potential effects on the therapy of nervous system disorders, particularly PD, but its specific underlying mechanism(s) remains poorly understood, leading to the great challenge of clinical application and management. Previous study has shown that acupuncture ameliorates PD motor symptoms and dopaminergic neuron damage by modulating intestinal dysbiosis, but its intermediate pathway has not been sufficiently investigated. A rat model of PD was induced using rotenone. The therapeutic effect of EA on PD was assessed using the pole and rotarod tests and immunohistostaining for tyrosine hydroxylase (TH) in the substantia nigra (SN) of brain. The role of gut microbiota was explored using 16S rRNA gene sequencing and metabonomic analysis. PICRUSt2 analysis, lipidomic analysis, LPS and inflammatory factor assays were used for subsequent exploration and validation. Correlation analysis was used to identify the key bacteria that EA regulates lipid metabolism to improve PD. The present study firstly reappeared the effects of EA on protecting motor function and dopaminergic neurons and modulation of gut microbial dysbiosis in rotenone-induced PD rat model. EA improved motor dysfunction (via the pole and rotarod tests) and protected TH+ neurons in PD rats. EA increased the abundance of beneficial bacteria such as Lactobacillus, Dubosiella and Bifidobacterium and decreased the abundance of Escherichia-Shigella and Morganella belonging to Pseudomonadota, suggesting that the modulation of gut microbiota by EA improving the symptoms of PD motility via alleviating LPS-induced inflammatory response and oxidative stress, which was also validated by various aspects such as microbial gene functional analysis, fecal metabolomics analysis, LPS and inflammatory factor assays and SNpc lipidomics analysis. Moreover, correlation analyses also verified strong correlations of Escherichia-Shigella and Morganella with motor symptoms and SNpc lipid peroxidation, explicating targets and intermediate pathways through which EA improve PD exercise symptom. Our results indicate that the improvement of motor function in PD model by EA may be mediated in part by restoring the gut microbiota, which intermediate processes involve circulating endotoxins and inflammatory mediators, SNpc oxidative stress and lipid peroxidation. The gut-microbiome - brain axis may be a potential mechanism of EA treatment for the PD.

Protocol for a randomized controlled trial exploring the brain mechanism and therapeutic effect of electroacupuncture on cognitive function and sleep quality in chronic insomnia

BackgroundInsomnia is a prevalent sleep disorder that affects up to 15% of the population worldwide and is the second most common mental health issue. There is increasing interest in the effects of long-term insomnia on cognitive function. Electroacupuncture can effectively improve cognitive function and sleep quality, yet the underlying brain network mechanisms remain unclear. This study aims to explore the network regulatory mechanisms associated with enhanced cognitive function and sleep quality, providing theoretical support for the use of electroacupuncture in the clinical treatment of chronic insomnia.MethodsThis study is divided into two parts. Sixteen individuals with chronic insomnia and 16 healthy controls of similar age and gender will be recruited in Study 1 to examine the brain network topology of individuals with chronic insomnia. Study 2 will be a randomized controlled trial with 120 chronic insomnia patients divided into three groups: Group A (electroacupuncture plus placebo drug), Group B (drug plus placebo electroacupuncture), and Group C (placebo electroacupuncture plus placebo drug). Participants will be exposed to 24 treatments over an 8-week period (3 times per week) and monitored for 12 additional weeks. The primary outcome measure will be changes in brainwave data from before to after the treatment. In addition, the Wisconsin Card Sorting Test and the Pittsburgh Sleep Quality Index will be utilized as secondary outcomes to measure from before to after treatment and during the follow-up. A correlation analysis will be conducted to explore links among modifications in brainwave patterns, Wisconsin Card Sorting Test scores, and Pittsburgh Sleep Quality Index scores. Additionally, any adverse events will be strictly monitored.DiscussionElectroacupuncture may represent an alternative treatment for chronic insomnia, and this trial is expected to reveal the brain mechanism by which electroacupuncture improves cognitive function and sleep quality in chronic insomnia patients.Trial registrationChiCTR2200060150 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 20 May 2022).

Participation of the nucleus tractus solitarius in the therapeutic effect of electroacupuncture on post-stroke dysphagia through the primary motor cortex.

Post-stroke dysphagia (PSD), a common and serious disease, affects the quality of life of many patients and their families. Electroacupuncture (EA) has been commonly used effectively in the treatment of PSD, but the therapeutic mechanism is still under exploration at present. We aim to investigate the effect of the nucleus tractus solitarus (NTS) on the treatment of PSD by EA at Lianquan (CV23) through the primary motor cortex (M1). C57 male mice were used to construct a PSD mouse model using photothrombotic technique, and the swallowing function was evaluated by electromyography (EMG) recording. C-Fos-positive neurons and types of neurons in the NTS were detected by immunofluorescence. Optogenetics and chemical genetics were used to regulate the NTS, and the firing rate of neurons was recorded via multichannel recording. The results showed that most of the activated neurons in the NTS were excitatory neurons, and multichannel recording indicated that the activity levels of both pyramidal neurons and interneurons in the NTS were regulated by M1. This process was involved in the EA treatment. Furthermore, while chemogenetic inhibition of the NTS reduced the EMG signal associated with the swallowing response induced by activation of M1 in PSD mice, EA rescued this signal. Overall, the NTS was shown to participate in the regulation of PSD by EA at CV23 through M1.

Electroacupuncture attenuates ketamine-induced neuronal injury in the locus coeruleus of rats through modulation of the CAMK II/CREB pathway

BackgroundKetamine, despite its efficacy in treating depression, raises concerns regarding safety due to potential abuse, cognitive impairment, and bladder toxicity. Ketamine can affect the locus coeruleus (LC) norepinephrine and attention networks. This study explored the protective effects of electroacupuncture (EA) on the LC of rats exposed to repeated administration of ketamine while investigating the potential role of the Calcium CaM-dependent protein kinase II (CAMK II)/ cAMP response element binding protein (CREB) pathway in mediating EA's impact on ketamine-induced neuronal injury in LC. MethodsRats were repeatedly injected intraperitoneally with ketamine hydrochloride (50 mg/kg) once daily for seven days. Subsequently, EA was performed at the acupoints “Zusanli” (ST36) and “Sanyinjiao” (SP-6) once daily following ketamine administration. The Morris water maze test was employed to assess behavioral changes in the rats. Neuronal injury was examined using Nissl staining, and the expression of CAMK II, CREB, and phospho-CREB (p-CREB) was evaluated through immunohistochemistry and western blotting. ResultsEA mitigated the cognitive and exploratory impairments and attenuated neuronal injury in the LC induced by repeated administration of ketamine. The expression of CAMK II and p-CREB proteins in the LC increased following 7 days of ketamine administration. However, EA treatment led to a downregulation of CAMK II and p-CREB expression. ConclusionRepeated administration of ketamine in male rats can lead to neuronal injury and neurobehavioral dysfunction. However, EA was found to ameliorate neurodegeneration in the LC and enhance neurobehavioral symptoms. This therapeutic effect of EA may be attributed to its modulation of the CAMKII/CREB pathway, thereby mitigating the aforementioned adverse effects.

Effect of electroacupuncture at ST36 on the cerebral metabolic kinetics of rheumatoid arthritis rats

Electroacupuncture (EA) has been shown to enhance the recovery of symptoms in rheumatoid arthritis (RA); however, the underlying mechanism remains unclear. Both the pathogenesis of RA and the therapeutic effects of EA are closely associated with the metabolic activity of the brain. In this study, we investigated the effect of EA at the “Zusanli” acupoint (ST36) on a rat model of collagen-induced rheumatoid arthritis (CIA). The results demonstrated that EA effectively alleviated joint swelling, synovial hyperplasia, cartilage erosion, and bone destruction in CIA rats. Additionally, the metabolic kinetics study revealed a significant increase in the 13C enrichment of GABA2 and Glu4 in the midbrain of CIA rats treated with EA. Correlation network analysis showed that changes in Gln4 levels in the hippocampus were strongly associated with the severity of rheumatoid arthritis. Immunofluorescence staining of c-Fos in the midbrain’s periaqueductal gray matter (PAG) and hippocampus demonstrated increased c-Fos expression in these regions following EA treatment. These findings suggest that GABAergic and glutamatergic neurons in the midbrain, along with astrocytes in the hippocampus, may play vital roles in the beneficial effects of EA on RA. Furthermore, the PAG and hippocampus brain regions hold potential as critical targets for future RA treatments. Overall, this study provides valuable insights into the specific mechanism of EA in treating RA by elucidating the perspective of cerebral metabolism.

Observation on Therapeutic Effects of Electroacupuncture on Polycystic Ovary Syndrome of Kidney Deficiency and Phlegm Dampness Type and Oxidative Stress Level

Observation on Therapeutic Effects of Electroacupuncture on Polycystic Ovary Syndrome of Kidney Deficiency and Phlegm Dampness Type and Oxidative Stress Level

Protective effects of electroacupuncture on polycystic ovary syndrome in rats: Down-regulating Alas2 to inhibit apoptosis, oxidative stress, and mitochondrial dysfunction in ovarian granulosa cells

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women at reproductive age. The therapeutic effect of electroacupuncture (EA) on PCOS has been revealed, while the anti-PCOS mechanisms of EA have not been fully explored. In this study, PCOS were induced in rats by daily injection with dehydroepiandrosterone (DHEA) for 20 days and EA treatment was performed for 5 weeks. The mRNA expression profiles in ovarian tissues from control, PCOS, and EA-treated rats were examined by high-throughput mRNA sequencing. 5'-aminolevulinate synthase 2 (Alas2), a vital rate-limiting enzyme of the heme synthesis pathway, was selected to be further studied. PCOS led to the upregulation of Alas2 mRNA, whereas EA treatment restored this change. In vitro, primary ovarian granulosa cells (GCs) were challenged with H2O2 to mimic the oxidative stress (OS) state in PCOS. H2O2 induced apoptosis, OS, mitochondrial dysfunction, as well as Alas2 overexpression in GCs, while lentivirus-mediated Alas2 knockdown evidently restrained the above impairments. In summary, this study highlights the crucial role of Alas2 in cell apoptosis, OS, and mitochondrial dysfunction of PCOS GCs and provides potential therapeutic candidates for further investigation on PCOS treatment.

Electroacupuncture alleviates traumatic brain injury by inhibiting autophagy via increasing IL-10 production and blocking the AMPK/mTOR signaling pathway in rats.

Autophagy, switched by the AMPK/mTOR signaling, has been revealed to contribute greatly to traumatic brain injury (TBI). Electroacupuncture (EA) is a promising therapeutic method for TBI, however, the underlying mechanism is still unclear. Herein, we hypothesize that the therapeutic effect of EA on TBI is associated with its inhibition on AMPK/mTOR-mediated autophagy. Sprague-Dawley rats were randomly divided into three groups: sham, TBI, and TBI + EA. TBI model was established by using an electronic controlled cortical impactor. Rats were treated with EA at 12h after modeling, 15min daily for 14 consecutive days. EA was applied at the acupuncture points Quchi (LI 11), Hegu (LI4), Baihui (GV20), Guanyuan (CV4), Zusanli (ST36) and Yongquan (KI1), using dense-sparse wave, at frequencies of 1Hz, and an amplitude of 1 mA. After 3, 7 and 14 days of modeling, the modified neurological severity scale (mNSS), rota rod system, and Morris Water Maze (MWM) test showed that EA treatment promoted neurological function recovery in TBI rats. Moreover, EA treatment alleviated brain edema, pathological damage, neuronal apoptosis in TBI rats. EA improved abnormal ultrastructure, including abnormal mitochondrial morphology and increased autophagosomes, in the brain neurons of TBI rats, as measured by transmission electron microscopy, and the concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). Western blot and immunohistochemistry (IHC) assays were performed to measure the protein levels of interleukin 10 (IL-10), autophagy-related proteins and key proteins in the AMPK/mTOR signaling pathway. EA treatment increased IL-10 production, inhibited the AMPK/mTOR signaling, and inhibited excessive autophagy in TBI rats. Additionally, AMPK inhibitor Compound C treatment had similar effects to EA. Both AMPK agonist AICAR and IL-10 neutralizing antibody treatments reversed the effects of EA on the related protein levels of autophagy and the AMPK/mTOR signaling pathway, and abolished the protective effects of EA on TBI rats. In conclusion, EA treatment promoted neurological function recovery and alleviated pathological damage and neuronal apoptosis in TBI rats through inhibiting excessive autophagy via increasing IL-10 production and blocking the AMPK/mTOR signaling pathway.

Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings.

Electroacupuncture (EA) could enhance neuroregeneration and posttraumatic conditions; however, the underlying regulatory mechanisms remain ambiguous. PDCD6 (programmed cell death 6) is an established proapoptotic regulator which is responsible for motoneuronal death. However, its potential regulatory role in post-spinal cord injury (SCI) regeneration has remained largely unknown. Further investigations are warranted to clarify the involvement of PDCD6 post-SCI recovery and the underlying mechanisms. In our study, based on bioinformatics prediction, we found that miR-34a-3p might be an upstream regulator miRNA for PDCD6, which was subsequently validated through combined utilization of the qRT-PCR, western blot, and dual-luciferase reporter system. Our in vitro results showed that miR-34a-3p might promote the in vitro differentiation of neural stem cell (NSC) through suppressing PDCD6 and regulating other important neural markers such as fibroblast growth factor receptor 1 (FGFR1), MAP1/2 (MAP kinase kinases 1/2), myelin basic protein (MBP), βIII-tubulin Class III β-tubulin (βIII tubulin), and glial fibrillary acidic protein (GFAP). Notably, in the post-SCI rat model, exogenous miR-34a-3p agomir obviously inhibited the expression of PDCD6 at the protein level and promoted neuronal proliferation, motoneurons regeneration, and axonal myelination. The restorations at cellular level might contribute to the improved hindlimbs functions of post-SCI rats, which was manifested by the Basso-Beattie-Bresnahan (BBB) locomotor test. The impact of miR-34a-3p was further promoted by EA treatment in vivo. Conclusively, this paper argues that a miR-34a-3p/PDCD6 axis might be a candidate therapeutic target for treating SCI and that the therapeutic effect of EA is driven through this pathway.

Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats

Background The pathogenesis of slow transit constipation (STC) is associated with exosomal miR-34c-5p. Electroacupuncture (EA) improves gastrointestinal motility in gastrointestinal disorders, especially STC. Our study aimed to explore the mechanism by which EA improves intestinal motility by modulating the release of exosomes and the transmission of exosomal miR-34c-5p. Methods Fifty rats were randomly divided into five groups. STC model rats were induced, and GW4869, the exosome release inhibitor, was used to inhibit the release of exosome. The serum exosomes were authenticated under a transmission electron microscope and nanoparticle tracking analysis. RT-qPCR detected the expression of miR-34c-5p in serum exosomes and colonic tissues. The fecal number in 24 hours, Bristol scores, and intestinal transit rates were used to assess intestinal motility. Subsequently, hematoxylin and eosin (H&E) staining was used to examine the colonic mucosal histology. Finally, the expression of stem cell factor (SCF) and receptor tyrosine kinase (c-Kit) protein was measured using immunohistochemistry staining. Results We found that EA upregulated exosomal miR-34c-5p in serum and downregulated miR-34c-5p in colonic tissues (P < 0.01). EA improved fecal numbers in 24 hours, Bristol scores, and intestinal transit rates in STC rats (P < 0.01). EA recovered the colonic histological structure and enhanced the expression of SCF and c-Kit protein (P < 0.01). The therapeutic effect of EA was attenuated after inhibiting the release of the exosome. Conclusion Our results indicated that EA improves intestinal motility in STC rats by transporting of exosomal miR-34c-5p targeting the SCF/c-Kit signaling pathway.

Meta-Analysis on the Effects of Electric Acupuncture on Neural Functional Recovery and Related Pathways of Rats after Spinal Cord Injury.

Background Spinal cord injury (SCI) is a type of damage to the central nervous system (CNS) caused by various factors. The secondary injury of SCI is more complicated. Studies have found that electroacupuncture can help the recovery of nerve function during spinal cord injury. Therefore, this study explored the efficacy of electroacupuncture on complications after spinal cord injury through meta-analysis. Methods Relevant literatures published from January 2010 to March 2022 were searched with “Electric acupuncture, Spinal cord injury, Neural functional recovery, Spinal cord injury in rats, Neuronal Signaling” as search words. The risk of bias of included references was analyzed and assessed using RevMan 5.3 software and Stata software. Heterogeneity between studies was assessed using the Q-test and heterogeneity (I2). Results There was no heterogeneity among the study groups. The comparison on the therapeutic effects of electroacupuncture and conventional therapy suggested that electroacupuncture was more effective for nerve recovery after spinal cord injury than conventional therapy. It can better improve the recovery of motor function after spinal cord injury in rats. On the other hand, SCI+EA had a good inhibitory effect on the expression of RhoA protein signal in rats and had a positive effect on the signal pathway. Discussion. The results of meta-analysis confirmed that electroacupuncture was more effective than conventional therapy in inhibiting pathways.

Influence of electroacupuncture of"Zusanli"(ST36)on mast cells/TRPV1 signaling pathway in visceral hypersensitivity rats with functional dyspepsia

To explore the interventional mechanism of electroacupuncture (EA) of "Zusanli"(ST36)based on the involvement of mast cells/ transient receptor potential vanilloid type1 (TRPV1) signaling pathway in relieving visceral hypersensitivity in functional dyspepsia (FD) rats. Sixty SD rats (half male and half female, 10 days in age) were randomly divided into normal control, model, medication (ketotifen) and EA groups, with 15 rats in each group. The FD model was established by gavage of iodoacetamide combined with tail clamping (stress stimulation). Rats of the medication group received intraperitoneal injection of ketotifen (1 mg·kg-1·d-1) for 14 d, and those of the EA group received EA of ST36 for 20 min, once a day for 14 d. An air-balloon was inserted into the rat's stomach for recording changes of the intragastric pressure (mL/mm Hg) via a pressure transducer. The visceral hypersensitivity was assessed using abdominal withdrawal reflex (AWR) score and the number and degranulation of mast cells of gastric mucosa were observed using toluidine blue staining. The expression levels of TRPV1 and proteinase activated receptor 2 (PAR2) in the stomach were observed using immunofluorescence histochemistry and Western blot, separately, and the contents of SP and CGRP in the stomach detected using ELISA. When the intragastric pressure was at 50, 60 and 70 mm Hg, the gastric compliance was significantly decreased (P<0.01), and the levels of visceral sensitivity increased in the model group （P<0.01）。 TRPV1 immunofluorescence tensity, expression of PAR2 and TRPV1 proteins, and contents of SP and CGRP in the stomach were considerably up-regulated in the model group compared with the normal control group (P<0.01). In comparison with the model group, under intragastric pressure of 50，60 and 70 mm Hg, the gastric compliance was obviously increased, and the visceral hypersensitivity decreased in the EA group （P<0.01,P<0.05）. TRPV1 immunofluorescence intensity, expression levels of PAR2 and TRPV1 proteins, and the contents of SP and CGRP in the stomach were considerably down-regulated in both medication and EA groups compared with the model group (P<0.01, P<0.05). The therapeutic effect of EA was significantly superior to that of medication in up-regulating the gastric compliance （at 70 mm Hg）, and down-regulating the contents of SP and CGRP (P<0.05). No significant differences were found between the EA and medication groups in up-regulating gastric compliance at intragastric pressure of 50 and 60 mm Hg, and in down-regulating the visceral sensitivity, TRPV1 fluorescence intensity, and expression of PAR2 and TRPV1 proteins (P>0.05). Toluidine blue staining showed an apparent increase of mast cell number with obvious degranulation in the gastric mucosa of rats in the model group, which was milder in the EA and medication groups. EA of ST36 can suppress visceral hypersensitivity and increase the gastric compliance in FD rats, which may be related with its effects in inhibiting the activation of gastric mast cells, and down-regulating the expression of gastric PAR2 and TRPV1 proteins and SP and CGRP contents.

Electroacupuncture Reduces Anxiety Associated With Inflammatory Bowel Disease By Acting on Cannabinoid CB1 Receptors in the Ventral Hippocampus in Mice

The therapeutic effects of electroacupuncture (EA) on the comorbidity of visceral pain and anxiety in patients with inflammatory bowel disease (IBD) is well known. It has been known that the ventral hippocampus (vHPC) and the cannabinoid type 1 receptors (CB1R) are involved in regulating anxiety and pain. Therefore, in this study, we determined whether EA reduces visceral pain and IBD-induced anxiety via CB1R in the vHPC. We found that EA alleviated visceral hyperalgesia and anxiety in TNBS-treated IBD mice. EA reversed over-expression of CB1R in IBD mice and decreased the percentage of CB1R-expressed GABAergic neurons in the vHPC. Ablating CB1R of GABAergic neurons in the vHPC alleviated anxiety in TNBS-treated mice and mimicked the anxiolytic effect of EA. While ablating CB1R in glutamatergic neurons in the vHPC induced severe anxiety in wild type mice and inhibited the anxiolytic effect of EA. However, ablating CB1R in either GABAergic or glutamatergic neurons in the vHPC did not alter visceral pain. In conclusion, we found CB1R in both GABAergic neurons and glutamatergic neurons are involved in the inhibitory effect of EA on anxiety but not visceral pain in IBD mice. EA may exert anxiolytic effect via downregulating CB1R in GABAergic neurons and activating CB1R in glutamatergic neurons in the vHPC, thus reducing the release of glutamate and inhibiting the anxiety circuit related to vHPC. Thus, our study provides new information about the cellular and molecular mechanisms of the therapeutic effect of EA on anxiety induced by IBD.

Effects of electroacupuncture on the expression of hypothalamic neuropeptide Y and ghrelin in pubertal rats with polycystic ovary syndrome.

BackgroundPolycystic ovary syndrome often starts in puberty, and its pathogenesis is not clear. This study aimed to explore the pathogenesis of pubertal polycystic ovary syndrome (PCOS) and assess the therapeutic effect of electroacupuncture on pubertal PCOS.MethodsDihydrotestosterone (DHT) was used to induce rat models of pubertal PCOS. pubertal rats with PCOS were randomly divided into a model group (M), an electroacupuncture group (EA), and a sham acupuncture group (SA). Age-matched normal rats were regarded as normal controls (N). Rats were treated with EA or SA five times a week for 25 minutes during their 6th–7th week. At the end of the experiment, we observed any changes in ovarian morphology; detected levels of metabolic indices in serum, the hypothalamus and pancreas.ResultsEA significantly improved estrous cycle disorders and the ovarian polycystic morphology in pubertal rats with PCOS, but SA only improved disorders of the estrous cycle. The serum levels of insulin, neuropeptide Y(NPY) and fasting blood glucose(FBG) increased significantly (both p < 0.01), while the serum levels of ghrelin(GHRL) decreased in the model group (p < 0.01). After treatment with EA, the levels of NPY (p < 0.01) and FBG (p < 0.05) went into decrease, whereas the levels of GHRL (p < 0.05) and insulin (p < 0.01) increased. There was few differences in the hypothalamic expression of galanin (GAL), galanin-like peptide (GALP) and ghrelin receptor(GHSR) between the four groups. The upregulation of NPY mRNA and neuropeptide Y2 receptor(NPY2R) mRNA and the downregulation of GHRL protein and mRNA in the hypothalamus, and the increased expression of NPY and NPY2R as well as the decreased expression of GHRL in the arcuate nucleus (ARC) can be rescued by EA. But, surprisingly, SA seem to make no difference to the levels of FBG and insulin, and the protein expression of ghrelin in the hypothalamus and ARC. Co-expression of kisspeptin and GHSR, and co-expression of gonadotrophin releasing hormone(GnRH) and NPY2R were observed in ARC. No differences were found between groups in protein of GAL, GALP and GHRL expression in the pancreas. Neither EA nor SA can attenuate the upregulated kisspeptin protein expression in the pancreas of PCOS model rats.ConclusionsEA and SA improved the symptoms of pubertal PCOS rats, and the mechanism might be associated with regulating hypothalamic NPY and ghrelin levels.

The modulatory effect of 100 Hz electroacupuncture on striatal synaptic plasticity in unilateral lesioned 6-OHDA rats

Recent studied have reported that impaired striatal synaptic plasticity played a crucial role in Parkinson’s disease (PD). Previous studies have suggested that electroacupuncture (EA) alleviated the motor deficits in PD patients and animal models. However, the mechanisms underlying this protection need to be further elucidated. In this study, we found that EA-induced improvement of motor deficits in the 6-hydroxydopamine (6-OHDA) rat model doesn’t act through dopaminergic system. EA rescued the decreased striatal long-term potentiation (LTP) in 6-OHDA rats. In addition, the declined expression of N-methyl-D-aspartic acid receptor subunit 2B (NR2B) in the striatum was remarkably up-regulated by EA. The EA-induced improvement of LTP can be eliminated by NR2B-selective inhibitor. It is indicated that EA-induced recovery of striatal LTP was correlated with the up-regulation of NR2B subunit. EA was also found to rescue the decreased dendritic arborization and the spine density in the striatum of 6-OHDA rats. Meanwhile, EA suppressed striatal glutamate content and vesicular glutamate transporter 1 which is expressed in cortico-striatal glutamatergic projections. The decrease of striatal glutamate content induced by decortication, EA treatment or a combination of both reversed the loss of striatal spine density in 6-OHDA rats. It is indicated that EA-induced reduction of cortico-striatal glutamate transmission contributes to the recovery of striatal spine density. In conclusion, the therapeutic effect of EA on the motor deficits of 6-OHDA rats was mediated by rescuing cortico-striatal glutamate transmission and striatal synaptic plasticity.

Electroacupuncture Ameliorates Cognitive Impairment Through the Inhibition of NLRP3 Inflammasome Activation by Regulating Melatonin-Mediated Mitophagy in Stroke Rats.

Previous studies found that electroacupuncture (EA) at the Shenting (DU24) and Baihui (DU20) acupoints alleviates cognitive impairment in cerebral ischemia-reperfusion (I/R) injury rats. Nonetheless, the mechanisms of the anti-inflammatory effects of EA are unclear. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO). Following I/R injury, the rats underwent EA therapy at the Shenting (DU24) and Baihui (DU20) acupoints for seven successive days. The Morris water maze test, magnetic resonance imaging (MRI) and molecular biology assays were utilized to assess the establishment of the rat stroke model with cognitive impairment and the therapeutic effect of EA. EA treatment of rats subjected to MCAO showed a significant reduction in infarct volumes accompanied by cognitive recovery, as observed in Morris water maze test outcomes. The possible mechanisms by which EA treatment attenuates cognitive impairment are by regulating endogenous melatonin secretion through aralkylamine N-acetyltransferase gene (AANAT, a rate-limiting enzyme of melatonin) synthesis in the pineal gland in stroke rats. Simultaneously, through melatonin regulation, EA exerts neuroprotective effects by upregulating mitophagy-associated proteins and suppressing reactive oxygen species (ROS)-induced NLRP3 inflammasome activation after I/R injury. However, melatonin receptor inhibitor (luzindole) treatment reversed these changes. The findings from this research suggested that EA ameliorates cognitive impairment through the inhibition of NLRP3 inflammasome activation by regulating melatonin-mediated mitophagy in stroke rats.

Effects of Electroacupuncture at Different Acupoints on Functional Dyspepsia Rats

Although, acupoint specificity is regarded as the core of scientific issues in electroacupuncture (EA), the difference of EA on treating functional dyspepsia (FD) at different acupoints is unclear. Therefore, this study aims to investigate the different therapeutic effects of EA at lower extremity or abdominal acupoints on the mucosal integrity and lower-inflammatory response in FD. The intragastric administration of iodoacetamide (IA) was performed in 48 rats to establish the FD model. These rats were randomly divided into the control group, the model group and the six EA groups receiving stimulation at the lower extremity (ST36, ST37, and ST39) or abdominal acupoints (ST25, CV4, and CV12) separately. The open-field test (OFT) was measured after 8 weeks of IA, and gastric emptying was evaluated after 10 days of the EA treatment. The local inflammation markers of CD45, eosinophil major basic protein (EMBP), and the tight junction proteins ZO1 and Claudin3 were assessed by immunofluorescence in all groups. Western blot analysis showed that the EMBP and Occludin1 levels in the duodenal. EA at lower extremity acupoint ST36 could improve the gastric emptying. EA at lower extremity acupoints reduced the immunoreactivity of EMBP, but the CD45 was reregulated by the ST37 and ST39 acupoints. The lower extremity acupoints also ameliorated FD-tight junction protein in the expression of Claudin3 and ZO1. However, only the ST36 suppressed the expression of EMBP and recovered the expression of Occludin1. Similarly, the effect of EA at abdominal acupoints was not obvious either in facilitating gastric motility or in improving inflammatory and mucosal injury. EA at lower extremity and abdominal acupoints with the same stimulation parameters had different therapeutic effects in gastric emptying, intestinal mucosal integrity, and inflammation response, thus proving the specificity of acupoints.