Acupuncture inhibits neuroinflammation an... - Cure Parkinson's

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Acupuncture inhibits neuroinflammation and gut microbial dysbiosis in a mouse model of Parkinson’s disease 2020

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I did not expect to see this type of action from acupuncture: Acupuncture inhibits neuroinflammation and gut microbial dysbiosis in a mouse model of Parkinson’s disease sciencedirect.com/science/a...

"Abstract

Growing evidences show that gut microbiota is associated with the pathogenesis of Parkinson’s disease (PD) and the gut-brain axis can be promising target for the development of the therapeutic strategies for PD. Acupuncture has been used to improve brain functions and inflammation in neurological disorders such as PD, and to recover the gastrointestinal dysfunctions in various gastrointestinal disorders. Thus, we investigated whether acupuncture could improve Parkinsonism and gut microbial dysbiosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. First, we observed that acupuncture treatment at acupoints GB34 and ST36 could improve motor functions and comorbid anxiety in PD mice. Next, we found that acupuncture increased the levels of dopaminergic fibers and neurons in the striatum and the substantia nigra, respectively. Acupuncture also restored the overexpression of microglia and astrocyte as well as conversion of Bax and Bcl-2 expression in both the striatum and the substantia nigra, indicating that inflammatory responses and apoptosis were blocked by acupuncture. Additionally, via 16S rRNA sequence analysis, we observed that the relative abundance of 18 genera were changed in acupuncture-treated mice compared to the PD mice. Of them, Butyricimonas, Holdemania, Frisingicoccus, Gracilibacter, Phocea, and Aestuariispira showed significant correlations with anxiety as well as motor functions. Furthermore, the predicted functional analyses showed that acupuncture restored the physiology functions such as glutathione metabolism, methane metabolism, and PD pathway. In conclusion, we suggest that the effects of acupuncture on the enhanced motor function and the protection of the dopaminergic neurons may be associated with the regulation of the gut microbial dysbiosis and thus the inhibition of the neuroinflammation in the PD mice."

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Acupuncture Attenuates Inflammation in Microglia of Vascular Dementia Rats by Inhibiting miR-93-Mediated TLR4/MyD88/NF-κB Signaling Pathway 2020 hindawi.com/journals/omcl/2...

"Abstract

Background. It is widely accepted that inflammation may contribute to cognitive impairment in patients with vascular dementia (VD). Our prior clinical researches have reported that acupuncture can alleviate cognitive function in VD, but the underlying mechanisms are still unclear. The purpose of this research was to explore whether acupuncture alleviates cognitive impairment by suppressing the microRNA-93- (miR-93-) mediated Toll-like receptor (TLR) signaling pathway, which triggers inflammatory responses in the central nervous system. Methods. VD was established by permanent bilateral common carotid artery occlusion in male Wistar rats. Three days after operation, the rats began daily treatment with acupuncture for two weeks. The levels of miR-93, Toll-like receptors (TLR2 and TLR4), intracellular signaling molecules (myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB)), and inflammatory cytokines were subsequently detected. TLR4 colocalized with neurons, microglia, and astrocytes in the hippocampus was evaluated. Neuroinflammation and cognitive function were determined after intracerebroventricular injection of TLR4 antagonist TAK-242 or agonist lipopolysaccharide (LPS) with or without acupuncture. Results. We found that acupuncture notably repressed the expression of inflammatory cytokines in the hippocampus and plasma of VD rats. The expression of TLR4, but not TLR2, was markedly downregulated by acupuncture, accompanied by a decrease in miR-93 and MyD88/NF-κB signaling pathway activation. The overexpression of TLR4 in microglia, but not in astrocytes and neurons, was reversed by acupuncture. Furthermore, intracerebroventricular injection of TAK-242 had similar effects to acupuncture on inflammation and cognitive function, while LPS injection abolished the beneficial effects of acupuncture. Conclusions. Taken together, these findings provide evidence that acupuncture attenuates cognitive impairment associated with inflammation through inhibition of the miR-93-mediated TLR4/MyD88/NF-κB signaling pathway in experimental VD. Acupuncture serves as a promising alternative therapy and may be an underlying TLR4 inhibitor for the treatment of VD."

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Bolt_Upright

Wow. Effects of Acupuncture on Neurological Disease in Clinical- and Animal-Based Research 2019 frontiersin.org/articles/10...

"Parkinson’s Disease

PD is the most common motor disorder in the world which is characterized by occult onset, slow progress and high disability. The main cause of the PD is the degeneration of dopaminergic neurons in the compact part of the substantia nigra (SN) and the decrease of dopamine biosynthesis in the remaining neurons, ultimately resulting in severe striatal dopamine deficiency and the development of primary motor symptoms. The pathogenesis of PD may be related to environmental factors, immunological abnormalities, mitochondrial dysfunction and oxidative stress. Because non-pharmacological therapies can improve PD symptoms to a certain extent and enchance the quality of life, about 40% of PD patients use at least one alternative therapies, acupuncture is one of the three most popular ASM treatment for PD patients (Rajendran et al., 2001; Dong et al., 2016).

Clinical Research on Acupuncture Treatment for PD

Chen et al. (2015) reported that combined with western medicine, acupuncture had integrated effects in reducing symptoms and signs of mind, behavior, mood, complications of therapy and depression in PD patients either short-term (18 weeks) or long-term (36 weeks) treatment. In another prospective randomized study, researchers found that the gait of PD patients improved significantly after 3 weeks of EA treatment (Lei et al., 2016). Rather clinical reports have found that acupuncture can improve complications caused by PD, such as lower urinary tract symptoms (Kim et al., 2018), fatigue (Corbin et al., 2016; Kong et al., 2018), rigidity and balance (Toosizadeh et al., 2015), swallowing reflex latency (Fukuda et al., 2016), sleep disorders (Landgren et al., 2011), and so on.

In other clinical studies, bee venom acupuncture have been reported to significantly reducing PD symptoms (Doo et al., 2015), improving PD rating scale including total score, the Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores parts II and III individually, as well as the berg balance scale, and the 30 min walking time (Cho et al., 2012), although the safety of bee venom acupuncture is uncertain. In a clinical study on evaluation of ASM for PD for 6-months, the researchers found that the Beck Depression Inventory (BDI) and the PD Questionnaire (PDQ-39) total score after acupoints such as St 42 (Chongyang) to Sp 3 (Taibai), LI 11 (Quchi), LI 15 (Jianyu), LI 20 (Yingxiang), ST 7 (Xiaguan), ST 36 (Tsu san li) treatment was improved, but the UPDRS motor scores worsened (Eng et al., 2006). A systematic review with meta-analysis included 11 RCTs with 831 subjects to assess the efficacy and safety of acupuncture combined with Madopar for PD (Liu et al., 2017). The results showed that acupuncture combined with Madopar can significantly improve the clinical effectiveness, the UPDRS II and UPDRS I–IV total summed scores, relieved gastrointestinal reactions, on-off phenomena and mental disorders but did not significantly reduce dyskinesia, compared with drug alone for the PD.

However, some RCTs and meta-studies have found that the effects of acupuncture for PD is not strong enough to be determined, and they speculated that the quality of trials was too low to draw any firm conclusions and suggested that the benefits of acupuncture may be due to non-specific effects (Cristian et al., 2005; Lee et al., 2013).

Animal-Based Research on Acupuncture Treatment for PD

With the extensive use of acupuncture as an ASM therapy for PD, the mechanisms based on animal model of acupuncture treatment for PD were widely investigated. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA) and rotenone are widely used as inducers in animal models of PD (Andrzejewski et al., 2019; Gai et al., 2019; He et al., 2019).

Neurotransmitters

Yu et al. (2016) demonstrated that EA is able to improve motor function and enhance dopamine availability in 6-OHDA-lesioned PD mice. Wang et al. (2018) showed that the EA alleviated motor symptoms and up-regulated vesicular glutamate transporter 1 (VGluT1) in the ipsilateral subthalamic nucleus (STN) of hemi-parkinsonian rats. Lin et al. (2017) found that EA at the GB34 (Yang ling quan) and LR3 (Tai chong) acupoints increased the latency to fall from the accelerating rotarod and improved striatal dopamine levels in the MPTP-lesioned mouse model. In addition, EA inhibited apomorphine-induced rotational behavior and locomotor activity in the MPP+-lesioned rat model. Laser acupuncture at HT7 enhanced memory and neuron density in CA3 and dentate gyrus and laser acupuncture also decreased acetylcholinesterase (AChE), monoamine oxidase B (MAO-B), and malondialdehyde (MDA) while increased glutathione peroxidase (GSH-Px) in the hippocampus of a 6-OHDA lesion rats (Wattanathorn and Sutalangka, 2014). With the development of protein and genomics technics recent years, proteomic analysis demonstrated that EA reversed six proteins in unlesioned and 19 proteins in lesioned motor cortex of PD model, compared to non-treatment group (Li M. et al., 2017). These targeted proteins may be involved in maintaining the balance of neurotransmitters.

Neuronal Survival

Further mechanism studies have confirmed that neuroprotective effects of EA via the activation of survival pathways of Akt (protein kinase B, PKB) and brain-derived neurotrophic factor (BDNF) in the SN region. Li M. et al. (2017) observed the proteomic changes in the motor cortex of 6-OHDA-induced PD model after EA treatment in 4 weeks. EA significantly improved spontaneous floor plane locomotion and rotarod performance. After acupuncture stimulation at SI3 or GB34 (Yang ling quan) of MPTP induced PD mice for 12 days, acupuncture treatment increased the dopaminergic neuronal survival via the nigrostriatal pathway, the expression of DJ-1, the activities of superoxide dismutase and catalase in the striatum (ST; Lee et al., 2018). In the latest study, researcher reported that acupuncture activates the hypothalamic melanin-concentrating hormone (MCH) biosynthesis in PD mice, which is potential of dopaminergic neuron protection via downstream pathways related to neuronal survival (Park et al., 2017). Jia Y. J. et al. (2017) found that EA improved the group II metabotropic glutamate receptor (mGluR2/3) protein expression and mGluR3 mRNA expression in the striatum of (6-OHDA)-lesioned rats, which may play a critical role in the pathogenesis of PD. Other studies discovered that acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN region. Further gene array analysis revealed 22 probes (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma) that were up-regulated while 17 probes (two annotated genes: 4921530L21Rik and Gm13931) that were down-regulated in MPTP animals (Yeo et al., 2015).

A systematic review of acupuncture treatment for PD in animal models by retrieving 57 articles suggest that acupuncture is an effective treatment for animal PD models, but there is insufficient evidence to determine whether sex differences exist (Lee et al., 2016). But in other studies, the results are completely contradictory, Yang et al.’s (2017) acupuncture stimulation at GB34 (Yang ling quan) in PD animal model for 5 days. Acupuncture treatment did not attenuate tyrosine hydroxylase-immunoreactive neuronal death, depletion of striatal dopamine levels, or reduced striatal tyrosine hydroxylase expression (Yang et al., 2017).

α-Synuclein

Stimulating at the acupoint of Yang ling quan (GB34) promoted the autophagic clearance of α-synuclein (α-syn) in PD mouse model. Further research discovered that acupuncture promotes mammalian target of rapamycin (mTOR) independent autophagic clearance of aggregation-prone proteins in vivo experiments (Tian et al., 2016).

Neuroinflammation

Furthermore, EA improved the neuro-inflammatory and motor phenotypes of mutant α-synuclein (α-syn) protein (A53T) mice multiple motor tests (Deng et al., 2015). Further study showed that EA suppressed tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) in the striatum and midbrain. Similarly, bee venom acupuncture therapy (BVA) suppressed TNF-α and IL-1β in PD animal (Khalil et al., 2015). Both Deng et al. (2015) and Lv et al. (2015) found that EA improved nuclear factor-E2-related factor-2 (Nrf2), and Nrf2-regulated antioxidant enzymes in PD model."

Gigi216 profile image
Gigi216 in reply to Bolt_Upright

I want to try acupuncture! We have an auricular acupuncturist near me, she is from China and her credentials are impressive

Gigi216 profile image
Gigi216 in reply to Gigi216

Dr Li Chun Huang is recognized as

the world's leading holistic functional

complementary alternative eastern

Auricular Acupuncture Medicine therapy

expert. She has received the Recognition of Mastery and

Lifetime Achievement Award at the World International

Symposium on Auricular Acupuncture Therapy and Chinese

Auricular Medicine. She has received a metal plaque award from

the President of Italy as recognition of the series of the

treatments given to him during his visits to China.

Bolt_Upright profile image
Bolt_Upright in reply to Gigi216

Make sure she knows where to put the needles (but seriously, see JayPwP's comment below):

Mouse
Gigi216 profile image
Gigi216 in reply to Bolt_Upright

I’d like to see improvement in my swallowing that would be so great 😃 I use acupressure fairly regularly and see some improvement but it doesn’t last long

Bolt_Upright profile image
Bolt_Upright

Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice 2021 onlinelibrary.wiley.com/doi...

"Abstract

Background

Postoperative cognitive dysfunction (POCD) is associated with worsened prognosis especially in aged population. Clinical and animal studies suggested that electroacupuncture (EA) could improve POCD. However, the underlying mechanisms especially EA’s regulatory role of inflammasomes remain unclear.

Methods

The model of POCD was established by partial hepatectomy surgery in 18-month mice with or without postoperative EA treatment to the Baihui acupoint (GV20) for 7 days. Cognitive functions were assessed by Morris water maze test, and proinflammatory cytokines IL-1β and IL-6 and microglia activity were assayed by qPCR, ELISA, or immunohistochemistry. Tight junction proteins, NLRP3 inflammasome and downstream proteins, and NF-κB pathway proteins were evaluated by western blotting.

Results

EA markedly preserved cognitive dysfunctions in POCD mice, associated with the inhibition of neuroinflammation as evidenced by reduced microglial activation and decreased IL-1β and IL-6 levels in brain tissue. EA also preserved hippocampal neurons and tight junction proteins ZO-1 and claudin 5. Mechanistically, the activation of NLRP3 inflammasome and NF-κB was inhibited by EA, while NLRP3 activation abolished EA’s treatment effects on cognitive function.

Conclusion

EA alleviates POCD-mediated cognitive dysfunction associated with ameliorated neuroinflammation. Mechanistically, EA’s treatment effects are dependent on NLRP3 inhibition."

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Bolt_Upright

Good podcast: How electric acupuncture zaps inflammation in mice 2021 nature.com/articles/d41586-...

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Bolt_Upright

Effect of Electroacupuncture on Gut Microbiota in Participants With Knee Osteoarthritis 2021 frontiersin.org/articles/10...

"Conclusion

Our study suggested that EA could significantly relieve KOA pain. Although gut microbiome might not be related to KOA, EA could improve the inflammatory effects by changing serval genera in gut microbiota. In particular, EA reduced the abundance of pathogenic bacteria, such as Streptococcus and increased the abundance of beneficial bacteria including Agathobacter and Bacteroide in the gut. Although we have no direct evidence that the bacteria changed by EA can relieve KOA pain, our clinical research still provides indirect evidence that gut microbiota may be involved in the treatment."

Bfp69 profile image
Bfp69

All your your posts point to the fact that you are an avid, passionate researcher for this community. Thanks for all the information! We just started weekly electric acupuncture a few weeks ago and are may be seeing some improvement. Sleeping better, walking with walker further, standing a little straighter. Also trying some traditional Chinese medicine from the ssme dr who has over 20 years experience and is very professional. We’ll see…

JayPwP profile image
JayPwP

healthunlocked.com/cure-par...

JayPwP profile image
JayPwP in reply to JayPwP

GB34, LR3, GV20 and now ST36. Will try Acupressure

ncbi.nlm.nih.gov/pmc/articl...

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