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Transmission electron microscope (TEM) images for neuron cells in each group(7th day after last MPTP injection).: Arrowheads: autophagosome; asterisk: mitochondria, Scale bar: 2 μm; inset: magnified image for mitochondria(Scale bar: 0.5 μm).
Source publication
Acupuncture has historically been practiced to treat medical disorders by mechanically stimulating specific acupoints with fine needles. Despite its well-documented efficacy, its biological basis remains largely elusive. In this study, we found that mechanical stimulation at the acupoint of Yanglingquan (GB34) promoted the autophagic clearance of α...
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Citations
... In 2016, a study established the correlation of acupuncture-based PD therapy with autophagy. It was observed that acupuncture on Yanglingquan (GB34) in the leg of a PD rat can distally regulate the autophagic level in the brain and promote the clearance of α-synuclein [29]. A later study employed atomic force microscopic tips to precisely control the force exerted on mammalian cells, which revealed that "nanoacupuncture" could trigger cell-specific autophagy [30]. ...
... Previous results showed that Xiaoxuming decoction could protect rat brain mitochondria, reduce structure damage and swelling of brain mitochondrial, improve mitochondrial respiration and mitochondrial membrane potential, and reduce the production of mitochondrial reactive oxygen species. 36 Some animal experiments also showed that acupuncture increased the autophagy clearance rate of αsynuclein through the m-TOR-independent pathway, and speculating that activating autophagy could inhibit the neurodegeneration of PD. 37 Neuroinflammation is a common pathological feature in neurodegenerative diseases. As the primary participant in the immune defense of the central nervous system, microglia release interleukins IL-1β, IL-6, TNF-α and other inflammatory mediators after activation. ...
Objective:
To explore the possible mechanism of Tongdu Tiaoshen acupuncture combined with Xiaoxuming decoction (, XXMD) in the treatment of Parkinson's disease (PD).
Methods:
C57BL/6 mice were randomly divided into eight groups ( 12), including blank group, model group, medication group, acupuncture group, high-dose XXMD group (XXMD-H), low-dose XXMD group (XXMD-L), acupuncture combined with high-dose XXMD group (A+H), and acupuncture combined with low-dose XXMD group (A+L). After treatment for 6 weeks, dopamine (DA) neurons and the pathological changes of tyrosine hydroxylase (TH) positive cells were observed. The enzyme-linked immunosorbent assay (ELISA) was used to measure the content of DA and the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α). The mRNA level of PINK1 and Parkin and the protein expression of Nix, PINK1 and Parkin in the substantia nigra were also detected.
Results:
Combination treatment effectively ameliorated the symptoms of PD. Compared with model group, combined treatment significantly up-regulated the protein expression of Nix, Parkin and PINK1 and the mRNA levels of PINK1 and Parkin in the substantia nigra (<0.0001, <0.001, <0.01 or <0.05). Furthermore, the levels of pro-inflammation cytokines were obviously decreased after combination therapy, while IL-10 content was increased remarkably (<0.01).
Conclusion:
Compared with each treatment alone, combination therapy improved the pathological damage of DA neurons of PD mice more effectively. The possible mechanism may be attributed to the up-regulated level of mitochondrial autophagy and improved mitochondrial function. These results provide fresh insight into the mechanism of co-treatment with Tongdu Tiaoshen acupuncture and XXMD for PD.
... We have demonstrated previously that acupuncture can promoted the autophagic clearance of α-synuclein (a wellknown aggregation-prone protein closely related to PD), improved the activity of dopaminergic neurons in SNpc, and improved the motor function at the behavior level of PD mice. 18 A recent meta-analyses have noted the positive effects of acupuncture combined with conventional treatment in reducing motor symptoms in PD (as measured by UPDRS II, III, IV and total score). 19 Another trial reported that acupuncture helped patients with PD with their quality of life and non-motor symptoms, such as fatigue, pain, sleep, and depression. ...
Background
Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD.
Methods
In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517.
Findings
At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of −9.1 points (95% CI, −11.8 to −6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR −26.0 to 0.0) in the EA group and 2.5 points (IQR: −11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient.
Interpretation
The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD.
Funding
Shanghai “Science and Technology Innovation Action Plan” Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).
... In the rotarod test, the durations that mice stayed on the rotating rod at rotation speeds of 10, 15, 20, 25, and 30 rpm were recorded, with a maximum residence time of 300 s at each rotation speed. e ORP score of each mouse was calculated using the trapezoidal method [56,57]. ...
Constipation is one of the most common nonmotor symptoms in patients with Parkinson’s disease (PD) and often occurs before motor symptoms. Electroacupuncture effectively improves the symptoms of constipation in patients with PD. In the present study, we used thymus cell antigen 1-α-synuclein (Thy1-αSyn) transgenic mice as a model of intestinal motility disorders in PD to determine the therapeutic effect of electroacupuncture and the underlying mechanisms. Electroacupuncture significantly improved fecal excretion and accelerated the rate of small-intestinal propulsion in Thy1-αSyn mice by upregulating the serotonin concentration and the expression of the serotonin 4 receptor. Consequently, the downstream cyclic AMP/protein kinase A (cAMP/PKA) pathway was affected, and to upregulate and downregulate, the expression of substance P was upregulated, and the expression of calcitonin gene-related peptide was downregulated. In summary, electroacupuncture improved intestinal motility in PD mice by affecting serotonin levels, serotonin 4 receptor expression, and the cAMP/PKA pathway, providing a potentially effective and promising complementary and alternative therapy for relieving constipation symptoms in patients with PD.
... Yeo et al. found that acupuncture at GB34 and LR3 upregulated serum/glucocorticoid-regulated kinase 1 (SGK1) and inhibited an α-syn production (36). Tian et al. (37) observed that microtubule-associated protein 1 light chain 3 II (LC3II) and lysosomal-associated membrane protein 1 (LAMP1) were reduced and more than 50% of α-syn in the SNpc was cleared after the treatment of acupuncture 4 days, suggesting that acupuncture at GB34 enhances degradation of α-syn and the clearance of autophagosomes. (2) Acupuncture inhibits the apoptotic pathways, thus promoting the survival of dopaminergic neurons. ...
Background
Acupuncture has been widely used in the treatment of patients with Parkinson's disease (PD) in the world. Despite we have an in-depth understanding of acupuncture in this field over the past years, there is no available literature on bibliometric analysis on the development of acupuncture on PD. This study was designed to explore the global trend in the research of acupuncture on PD in the recent 20 years by the software CiteSpace (5.8.R3) and VOSviewer (1.6.14).
Methods
Publications regarding acupuncture therapy for PD from 2000 to 2021 were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to analyze the number of publications, the contribution of countries, institutions, journals, authors, references, and keywords.
Results
A total of 217 studies were extracted from the database. The outputs of the publications in this field showed an upward trend during the past two decades. The country and institutions with the most publications in this field are China, South Korea, and the USA. They were the main contributors to the research. Kyung Hee University and Capital Medical University were the two most productive organizations. Hi-Joon Park had made the greatest contributions to the field. Evidence-based Complementary and Alternative Medicine was the most popular journals in this field. “Electroacupuncture” and “Bee venom acupuncture” were emerging research hotspots.
Conclusion
The research on acupuncture on PD is potential. Authors from different countries/regions and organizations need to remove the language and academic barriers to enhance global cooperation and communications. Scholars in this field need to publish their research findings in high-quality journals to gain more attention worldwide. This study indicated that the mechanism leading to the non-motor symptoms of PD, the establishment of appropriate models that fully reflects the non-motor features of human PD, and the efficacy and safety of promising therapies for patients with PD will remain research frontiers in the future.
... Second, acupuncture activated the MCH in the LH involved in neuronal protection by upregulating the downstream pathways related to neuroprotection in the SN (Park et al., 2017). Third, acupuncture also produced antioxidant, antiinflammatory, and autophagy control (Kang et al., 2007;Tian et al., 2016;Lee et al., 2018). The exact mechanism of decrease of c-Fos in those regions needs to be further elucidated. ...
Parkinson’s disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms.
... [17][18][19][20] Acupuncture stimulation has proven to protect dopaminergic neurons and improve the motor control ability of PD in experimental and clinical study. 15,[21][22][23] It was reported that acupuncture at Yanglingquan acupoints (GB34) could promote the autophagic clearance of alphasynuclein protein to alleviate the symptoms of 1-methyl-4-phenyl-1,-2,3,6-tetrahydropyridine (MPTP)-induced PD. 24 Several studies have shown that acupuncture antioxidative effects in PD mouse model. [25][26][27][28] Although acupuncture can protect dopaminergic neurons against oxidative damage, it remains unclear about the in situ information of biochemical components in dopaminergic neurons. ...
... 34,35 Mice in the acupuncture group were stimulated with acupuncture at GB34 acupoints once a day for 12 days according to a previous study. 24 GB34 is an acupoint of the gall bladder meridian, which is located at the depression anterior and inferior to the fibular head of leg. The acupuncture needle (10 mm in length, 0.19 mm in diameter) was inserted to a depth of 3 mm at GB34 acupoints. ...
... The overall rotarod performance score was calculated according to previous study. 24 ...
Objectives:
Acupuncture stimulation has proven to protect dopaminergic neurons from oxidative damage in animal models of Parkinson's disease (PD), but it remains unclear about the in situ information of biochemical components in dopaminergic neurons. Here, we aimed to analyse in situ changes of biochemical components and lipid peroxidation levels in dopaminergic neurons in PD mice treated with acupuncture by synchrotron FTIR micro-spectroscopy technique.
Materials and methods:
About 9-10-week-old C57BL/6 mice were used to establish PD model by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg for 5 days). Acupuncture stimulation was performed once a day for 12 days. Behaviour test was determined using the rotarod instrument. Biochemical compositions of dopaminergic neurons in substantia nigra pars compacta were analysed by synchrotron FTIR micro-spectroscopy technique. The number and ultrastructure of dopaminergic neurons were respectively observed by immunofluorescence and transmission electron microscopy (TEM).
Results:
We found that the number and protein expression of dopaminergic neurons in MPTP-treated mice were reduced by about half, while that in the mice treated by acupuncture were significantly restored. Acupuncture treatment also restored the motor ability of PD mice. The results of single cell imaging with synchrotron FTIR micro-spectroscopy technique showed that the proportion of lipid in MPTP treated mice increased significantly. Especially the ratio of CH2 asymmetric stretching and CH3 asymmetric stretching increased significantly, suggesting that MPTP induced lipid peroxidation damage of dopaminergic neurons. It is also supported by the result of TEM, such as mitochondrial swelling or atrophy, loss of mitochondrial crests and mitochondrial vacuolization. Compared with MPTP treated mice, the proportion of lipid in acupuncture treated mice decreased and the mitochondrial structure was restored.
Conclusions:
Acupuncture can inhibit the level of lipid peroxides in dopaminergic neurons and protect neurons from oxidative damage. The study provides a promising method for in situ analysis of biochemical compositions in PD mice and reveals the mechanism of acupuncture in treating neurodegenerative diseases.
... 23 It has been shown that EA can regulate autophagy; Wu et al. 24 verified that EA pretreatment can induce tolerance against cerebral ischemia/reperfusion injury through inhibition of the autophagy pathway, while its neuroprotective effects were reversed by the autophagy inducer rapamycin. Tian et al. 25 found that EA can promote mammalian target of rapamycin (mTOR)-independent autophagic clearance of aggregation-prone proteins in mouse brain. Both acupuncture and moxibustion have been shown to accelerate the autophagic clearance of α-syn and improve behavioral performance in a rat model of Parkinson's disease, which may be associated with suppression of the mTOR/p70S6K pathway. ...
Background
Increasing evidence shows that miRNAs contribute to the establishment and development of obesity by affecting many biological and pathological processes, such as adipocyte differentiation, hepatic lipid metabolism, insulin resistance, and neurological regulation of obesity. As a clinical intervention approach, acupuncture has been shown to be effective in the treatment of obesity and other metabolic diseases. Our previous whole genome study in central nervous system (CNS)-specific Stat5 knockout (KNO) obese mice found that electroacupuncture (EA) could reduce body weight and promote white browning.
Objective
To clarify the effect of EA on miRNAs and understand how it regulates gene expression.
Methods
Twelve-week-old male Stat5NKO mice with body weight 20% greater than that of Stat5fl/fl (control) mice were divided into a Stat5NKO (model) group and EA-treated Stat5NKO + EA group. A cohort of Stat5fl/fl mice of the same age were included as the control group. EA was administered under isoflurane anesthesia at unilateral ST36 and ST44 daily (left and right sides were treated every other day), 6 times per week for a total of 4 weeks. The miRNA profile was generated and miRNA regulatory networks were analyzed in the Stat5 nestin-cre mice before and after EA treatment. Autophagy-related proteins in adipocytes were detected after over-expression of miR27a.
Results
EA altered abnormal miRNA expression, including miRNA27a expression, and reduced the autophagy-related proteins ATG5 and ATG12.
Conclusion
We found that EA could regulate miRNA27a-mediated autophagy-related proteins and promote white fat browning, which may contribute to weight loss. To our knowledge, this is the first report of miRNAs potentially driving the effect of EA on white fat browning through the autophagy process.
... Our previous study revealed that acupuncture can improve recovery of neural stem cells after ICH. 17 Acupuncture has also been shown to improve ICH-induced neurological deficits. 18 The ability of acupuncture to regulate autophagy has been documented in animal models of various brain diseases, including ischemic stroke, [19][20][21][22] Parkinson's disease, 23 and Alzheimer's disease. 24 Whether the same is true in ICH remains to be determined. ...
... 20,21 In a rat model of Parkinson's disease, however, acupuncture up-regulates LC3 and autophagy-associated protein lysosomal-associated membrane protein 1 (LAMP-1) and inhibits mTOR signaling, thereby enhancing autophagic clearance of α-synuclein. 23 It is possible that acupuncture inhibits autophagy when autophagy activity is high, and stimulates it when autophagy activity is relatively low, at least in nervous system diseases. Further studies should explore the factors modulating the effects of acupuncture on autophagy in ICH. ...
Background
Intracerebral hemorrhage (ICH) accounts for approximately 15% of all stroke cases. Previous studies suggested that acupuncture may improve ICH-induced neurological deficits. Therefore, we investigated the effects of acupuncture on neurological deficits in an animal model of ICH.
Methods
Adult male Sprague–Dawley rats were injected with autologous blood (50 μL) into the right caudate nucleus. Additional rats underwent sham surgery as controls. ICH rats either received acupuncture (GV20 through GB7 on the side of the lesion) or sham acupuncture (1 cm to the right side of the traditional acupuncture point locations). Some ICH rats received acupuncture plus rapamycin injection into the right lateral ventricle. Neurological deficits in the various groups were assessed based on composite neurological score. The perihemorrhagic penumbra was analyzed by histopathology following hematoxylin–eosin staining. Levels of autophagy-related proteins light chain (LC)3 and p62 as well as of mammalian target of rapamycin (mTOR)-related proteins, and phosphorylated (p)-mTOR and p-S6K1 (ribosomal protein S6 kinase beta-1), were assessed by Western blotting.
Results
Acupuncture significantly improved composite neurological scores 7 days after ICH (17.7 ± 1.49 vs 14.8 ± 1.32, p < 0.01). Acupuncture augmented autophagosome and autolysosome accumulation based on transmission electron microscopy. Acupuncture significantly increased expression of LC3 (p < 0.01) but decreased expression of p62 (p < 0.01). Acupuncture also reduced levels of p-mTOR and p-S6K1 (both p < 0.01).
Conclusion
Acupuncture improved neurological deficits in a rat model of ICH, possibly by inhibiting the mTOR pathway and activating autophagy.
... Autophagy is essential for the removal of toxic α-syn aggregates in order to maintain intracellular homeostasis [81]. Mammalian target of rapamycin (mTOR) is a negative regulator of cellular autophagy and it has been shown that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) upregulates microtubule-associated protein 1 light chain 3 II (LC3-II) in a PD model, while downregulation lysosomal-associated membrane protein 1 (LAMP1, lysosomal structural protein) indicates that an impairment of lysosomes and the interruption of autophagosome-lysosome fusion may lead to an accumulation of autophagosomes in the substantia nigra pars compacta (SNpc) of MPTP mice [58]. Tian et al. observed that after acupuncture treatment for 4 days, LC3-II was reduced by approximately 40% and LAMP1 by approximately 20%, and more than 50% of α-syn in the SNpc was cleared, suggesting that acupuncture at GB34 restores lysosomal structures and reduces the accumulation of autophagosomes, enhancing the clearance of autophagosomes and degradation of α-syn. ...
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.
