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Electroacupuncture Improves Neuronal Damage and Mitochondrial Dysfunction Through the TRPC1 and SIRT1/AMPK Signaling Pathways to Alleviate Parkinson’s Disease in Mice

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disease that mainly manifests as cognitive decline and motor dysfunction, the treatment of which is still a major challenge in the clinical field. Acupuncture therapy has been shown in many studies to enhance the body’s own immunity and disease resistance. This study mainly discusses the specific mechanism underlying electroacupuncture intervention in improving PD. Male C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a mouse PD model, and the chorea trembling control area of the head of PD mice was treated by electroacupuncture. Western blotting was used to detect the expression of related proteins in mouse pathological samples; TUNEL measured neuronal apoptosis levels; Nissl staining observed neuronal damage; immunofluorescence and immunohistochemistry were used to detect the expression of Iba-1, TH, and α-syn in substantia nigra denser (SN). The expression levels of oxidative stress factors and inflammatory factors were measured by kits. Flow cytometry measured mitochondrial membrane potential and Ca2+ levels. MPTP intraperitoneal injection induced an increase in inflammatory factors in PD mice and promoted the oxidative stress response, and the inflammatory response was alleviated after electroacupuncture treatment. Electroacupuncture intervention effectively alters the decrease in oxidative stress levels and alleviates neuronal damage in PD mice. Electroacupuncture improves mitochondrial dysfunction induced by MPTP in PD mice by activating the SIRT1/AMPK signaling pathway. We also confirmed that knocking down TRPC1 can inhibit the SIRT1/AMPK signaling pathway, weaken the Ca2+ content in mouse neuronal tissue, and promote cell apoptosis. Electroacupuncture improves neuronal damage and alleviates PD in mice through the TRPC1 and SIRT1/AMPK signaling pathways. In addition, electroacupuncture therapy can improve MPTP-induced mitochondrial dysfunction in PD mice and alleviate the PD process.

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Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  • Amores-Bonet L, Kleener R, Theis T et al (2022) Interactions between the polysialylated neural cell adhesion molecule and the transient receptor potential canonical channels 1, 4, and 5 induce entry of Ca(2+) into neurons [J]. Int J Mol Sci 23(17):10027

  • Arshad A, Chen X, Cong Z et al (2014) TRPC1 protects dopaminergic SH-SY5Y cells from MPP+, salsolinol, and N-methyl-(R)-salsolinol-induced cytotoxicity [J]. Acta Biochim Biophys Sin (shanghai) 46(1):22–30

    Article  CAS  PubMed  Google Scholar 

  • Bair AM, Thippegowda PB, Freichel M et al (2009) Ca2+ entry via TRPC channels is necessary for thrombin-induced NF-kappaB activation in endothelial cells through AMP-activated protein kinase and protein kinase Cdelta [J]. J Biol Chem 284(1):563–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cantó C, Gerhart-Hines Z, Feige JN et al (2009) AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity [J]. Nature 458(7241):1056–60

  • Chao CC, Huang CL, Cheng JJ et al (2022) SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson’s disease [J]. Redox Biol 58:102534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen M, Peng L, Gong P et al (2021) Baicalein induces mitochondrial autophagy to prevent Parkinson’s disease in rats via miR-30b and the SIRT1/AMPK/mTOR pathway [J]. Front Neurol 12:646817

    Article  PubMed  Google Scholar 

  • Eldeeb MA, Thomas RA, Ragheb MA et al (2022) Mitochondrial quality control in health and in Parkinson’s disease [J]. Physiol Rev 102(4):1721–1755

    Article  CAS  PubMed  Google Scholar 

  • Esteves M, Abreu R, Fernandes H et al (2022) MicroRNA-124-3p-enriched small extracellular vesicles as a therapeutic approach for Parkinson’s disease [J]. Mol Ther 30(10):3176–3192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gai C, Qiang T, Zhang Y et al (2021) Electroacupuncture in treatment of Parkinson disease: a protocol for meta-analysis and systematic review [J]. Medicine 100(3):e23010

    Article  PubMed  PubMed Central  Google Scholar 

  • He XL, Li XZ, Xu DW et al (2023) Electroacupuncture intervention improves lipid metabolism and promotes browning of white adipose tissue by activating AMPK/Sirt1 pathway and up-regulating Nrg4 content in middle-aged and aged obese rats [J]. Zhen ci yan jiu = Acupunct Res 48(8):764–72

  • Heckman CA, Ademuyiwa OM, Cayer ML (2022) How filopodia respond to calcium in the absence of a calcium-binding structural protein: non-channel functions of TRP [J]. Cell Commun Signal 20(1):130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann RF, Jonker MR, Brandenburg SM et al (2019) Mitochondrial dysfunction increases pro-inflammatory cytokine production and impairs repair and corticosteroid responsiveness in lung epithelium [J]. Sci Rep 9(1):15047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Liu Z, Li N et al (2022) Parkinson’s disease derived exosomes aggravate neuropathology in SNCA*A53T Mice [J]. Ann Neurol 92(2):230–245

    Article  CAS  PubMed  Google Scholar 

  • Huang K, Bao CL, Chen WW et al (2021) Effect of electroacupuncture on mitochondrial function in mice with Parkinson’s disease [J]. Zhen ci yan jiu = Acupunct Res 46(1):21–6

  • Jin M, Matsumoto S, Ayaki T et al (2022) DOPAnization of tyrosine in α-synuclein by tyrosine hydroxylase leads to the formation of oligomers [J]. Nat Commun 13(1):6880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam CH, Cheung JK, Tse DY et al (2022) Proteomic profiling revealed mitochondrial dysfunction in photoreceptor cells under hyperglycemia [J]. Int J Mol Sci 23(21):13366

  • Lee EJ, Choi Y, Lee HJ et al (2022) Human neural stem cell-derived extracellular vesicles protect against Parkinson’s disease pathologies [J]. J Nanobiotechnology 20(1):198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee Y, Lee H, Bae CH et al (2023) Electroacupuncture at GB34 modulates neurogenesis and BDNF-ERK signaling in a mouse model of Parkinson’s disease [J]. J Tradit Complement Med 13(3):263–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin JG, Chen CJ, Yang HB et al (2017) Electroacupuncture Promotes recovery of motor function and reduces dopaminergic neuron degeneration in rodent models of Parkinson’s disease [J]. Int J Mol Sci 18(9):1846

  • Lizama BN, Chu CT (2021) Neuronal autophagy and mitophagy in Parkinson’s disease [J]. Mol Aspects Med 82:100972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Z, Sun GF, Pan XA et al (2022) BCATc inhibitor 2 ameliorated mitochondrial dysfunction and apoptosis in oleic acid-induced non-alcoholic fatty liver disease model [J]. Front Pharmacol 13:1025551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maher P, van Leyen K, Dey PN et al (2018) The role of Ca(2+) in cell death caused by oxidative glutamate toxicity and ferroptosis [J]. Cell Calcium 70:47–55

    Article  CAS  PubMed  Google Scholar 

  • Mohamad KA, El-Naga RN, Wahdan SA (2022) Neuroprotective effects of indole-3-carbinol on the rotenone rat model of Parkinson’s disease: impact of the SIRT1-AMPK signaling pathway [J]. Toxicol Appl Pharmacol 435:115853

    Article  CAS  PubMed  Google Scholar 

  • Nguyen M, Wong YC, Ysselstein D et al (2019) Synaptic, mitochondrial, and lysosomal dysfunction in Parkinson’s disease [J]. Trends Neurosci 42(2):140–149

    Article  CAS  PubMed  Google Scholar 

  • Olsen AL, Clemens SG, Feany MB (2022) Nicotine-mediated rescue of α-synuclein toxicity requires synaptic vesicle glycoprotein 2 in drosophila [J]. Mov Disord 38(2):244–255

  • Paul S, Fatihi S, Sharma S et al (2022) Cyclin-dependent kinase 5 regulates cPLA2 activity and neuroinflammation in Parkinson’s disease [J]. eNeuro 9(6):ENEURO.0180–22.2022

  • Selvaraj S, Sun Y, Watt JA et al (2012) Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling [J]. J Clin Invest 122(4):1354–1367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song LZ, Li Y, Qian X et al (2022) Parkinson’s disease constipation effect of electroacupuncture at ST25 through colonic motility and enteric neuropathology [J]. Front Neurol 13:1092127

    Article  PubMed  Google Scholar 

  • Stephenson J, Nutma E, van der Valk P et al (2018) Inflammation in CNS neurodegenerative diseases [J]. Immunology 154(2):204–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Y, Zhang H, Selvaraj S et al (2017) Inhibition of L-type Ca(2+) channels by TRPC1-STIM1 complex is essential for the protection of dopaminergic neurons [J]. J Neurosci 37(12):3364–3377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaidya B, Sharma SS (2020) Transient receptor potential channels as an emerging target for the treatment of Parkinson’s disease: an insight into role of pharmacological interventions [J]. Front Cell Dev Biol 8:584513

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang H, Cheng X, Tian J et al (2020) TRPC channels: Structure, function, regulation and recent advances in small molecular probes [J]. Pharmacol Ther 209:107497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu J, Lu AD, Zhang LP et al (2019) Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia] [J. Zhonghua Xue Ye Xue Za Zhi 40(1):52–57

    CAS  PubMed  Google Scholar 

  • Wu S, Zou MH (2020) AMPK, mitochondrial function, and cardiovascular disease [J]. Int J Mol Sci 21(14):4987

  • Xu N, Meng H, Liu T et al (2018) TRPC1 deficiency exacerbates cerebral ischemia/reperfusion-induced neurological injury by potentiating Nox4-derived reactive oxygen species generation [J]. Cell Physiol Biochem 51(4):1723–1738

    Article  CAS  PubMed  Google Scholar 

  • Yang S, Wu GL, Li N et al (2022) A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy [J]. J Nanobiotechnology 20(1):475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Y, Zhan X, Cong Y et al (2016) The role of TRP and trkA signal transduction pathways in the neuroprotective mechanism of electroacupuncture in Parkinson’s disease [M]. Weihai Wendeng Central Hospital

  • Zhang C, Zhao M, Wang B et al (2021) The Nrf2-NLRP3-caspase-1 axis mediates the neuroprotective effects of celastrol in Parkinson’s disease [J]. Redox Biol 47:102134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang N, Yu X, Song L et al (2022) Ferritin confers protection against iron-mediated neurotoxicity and ferroptosis through iron chelating mechanisms in MPP(+)-induced MES23.5 dopaminergic cells [J]. Free Radic Biol Med 193(Pt 2):751–763

  • Zhao Y, Luo D, Ning Z et al (2019) Electro-acupuncture ameliorated MPTP-induced parkinsonism in mice via TrkB neurotrophic signaling [J]. Front Neurosci 13:496

    Article  PubMed  PubMed Central  Google Scholar 

  • Zou Y, Chen Z, Sun C et al (2021) Exercise intervention mitigates pathological liver changes in NAFLD zebrafish by activating SIRT1/AMPK/NRF2 Signaling [J]. Int J Mol Sci 22(20):10940

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Funding

This study was supported by Geng Xin, a Project for the Training of Technological Innovation Talents in Yunnan Province (202205AD160006); the Associated Project of Yunnan Province Science & Technology Department and Kunming Medical University Basic Research for Application (202301AY070001-209); the subproject of the Special Fund for Applied Basic Research of The Center for Diagnosis and Treatment of Neurological Diseases in Yunnan Province (ZX2019-03-05); the Major Science and Technology Special Project of Yunnan Province (202102AA100061); the PhD Research Fund of the First Affiliated Hospital of Kunming Medical University (2020BS019); and the PhD Research Fund of the First Affiliated Hospital of Kunming Medical University (2022BS015).

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Author notes

  1. Xin Geng and Yanghong Zou contributed equally to this study.

Authors and Affiliations

  1. The Second Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China

    Xin Geng, Yanghong Zou, Tao Huang, Shipeng Li & Hualin Yu

  2. Yunnan Provincial Clinical Research Center for Neurological Disease, Kunming, 650032, Yunnan, China

    Xin Geng, Yanghong Zou, Tao Huang, Shipeng Li, Ailan Pang & Hualin Yu

  3. Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China

    Ailan Pang

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  1. Xin Geng
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Contributions

All authors contributed substantially to this manuscript. Conceptualization: XG and YZ; methodology: XG and TH; software: YZ and SL; validation: XG; formal analysis: SL and AP; investigation: XG, YZu, and HY; resources: HY; writing—original draft preparation: XG and YZ; writing—review and editing: HY; visualization: TH and AP; supervision: HY; funding acquisition: HY. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Hualin Yu.

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Ethics Approval and Consent to Participate

All animal experimental protocols were approved by the Animal Ethics Review Committee of Kunming Medical University (approval number kmmu2021718). The animal procedures adhered to the ARRIVE guidelines 2.0.

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The authors declare no competing interests.

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Geng, X., Zou, Y., Huang, T. et al. Electroacupuncture Improves Neuronal Damage and Mitochondrial Dysfunction Through the TRPC1 and SIRT1/AMPK Signaling Pathways to Alleviate Parkinson’s Disease in Mice. J Mol Neurosci 74, 5 (2024). https://doi.org/10.1007/s12031-023-02186-z

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