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Neuroscience Bulletin

, Volume 34, Issue 3, pp 476–484 | Cite as

Electroacupuncture Alleviates Motor Symptoms and Up-Regulates Vesicular Glutamatergic Transporter 1 Expression in the Subthalamic Nucleus in a Unilateral 6-Hydroxydopamine-Lesioned Hemi-Parkinsonian Rat Model

  • Yanyan Wang
  • Yong Wang
  • Junhua Liu
  • Xiaomin Wang
Original Article

Abstract

Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson’s disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.

Keywords

Parkinson’s disease Electroacupuncture Motor behavior Vesicular glutamate transporter 1 

Notes

Acknowledgements

This work was supported by the Beijing Municipal Science and Technology Commission (Z161100002616007), the National Key Research and Development Program (2016YFC1306300), the Major Program of the National Natural Science Foundation of China (81527901), and the Natural Science Foundation of Beijing Municipality (7082008).

Compliance with Ethical Standards

Conflict of interest

All authors claim that there are no conflicts of interest.

References

  1. 1.
    Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 1973, 20: 415–455.CrossRefPubMedGoogle Scholar
  2. 2.
    Dewey RB, Jr. Management of motor complications in Parkinson’s disease. Neurology 2004, 62: S3–S7.CrossRefPubMedGoogle Scholar
  3. 3.
    Saint-Cyr JA, Taylor AE, Lang AE. Neuropsychological and psychiatric side effects in the treatment of Parkinson’s disease. Neurology 1993, 43: S47–S52.PubMedGoogle Scholar
  4. 4.
    Liang XB, Liu XY, Li FQ, Luo Y, Lu J, Zhang WM, et al. Long-term high-frequency electro-acupuncture stimulation prevents neuronal degeneration and up-regulates BDNF mRNA in the substantia nigra and ventral tegmental area following medial forebrain bundle axotomy. Brain Res Mol Brain Res 2002, 108: 51–59.CrossRefPubMedGoogle Scholar
  5. 5.
    Sun Z, Jia J, Gong X, Jia Y, Deng J, Wang X, et al. Inhibition of glutamate and acetylcholine release in behavioral improvement induced by electroacupuncture in parkinsonian rats. Neurosci Lett 2012, 520: 32–37.CrossRefPubMedGoogle Scholar
  6. 6.
    Jia J, Sun Z, Li B, Pan Y, Wang H, Wang X, et al. Electro-acupuncture stimulation improves motor disorders in Parkinsonian rats. Behav Brain Res 2009, 205: 214–218.CrossRefPubMedGoogle Scholar
  7. 7.
    Jia J, Li B, Sun ZL, Yu F, Wang X, Wang XM. Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats. Behav Neurosci 2010, 124: 305–310.CrossRefPubMedGoogle Scholar
  8. 8.
    Deng J, Lv E, Yang J, Gong X, Zhang W, Liang X, et al. Electroacupuncture remediates glial dysfunction and ameliorates neurodegeneration in the astrocytic alpha-synuclein mutant mouse model. J Neuroinflammation 2015, 12: 103–116.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Liu XY, Zhou HF, Pan YL, Liang XB, Niu DB, Xue B, et al. Electro-acupuncture stimulation protects dopaminergic neurons from inflammation-mediated damage in medial forebrain bundle-transected rats. Exp Neurol 2004, 189: 189–196.CrossRefPubMedGoogle Scholar
  10. 10.
    Lv E, Deng J, Yu Y, Wang Y, Gong X, Jia J, et al. Nrf2-ARE signals mediated the anti-oxidative action of electroacupuncture in an MPTP mouse model of Parkinson’s disease. Free Radic Res 2015, 49: 1296–1307.CrossRefPubMedGoogle Scholar
  11. 11.
    Wang HM, Pan YL, Xue B, Wang X, Zhao F, Jia J, et al. The antioxidative effect of electro-acupuncture in a mouse model of Parkinson’s disease. PLoS One 2011, 6: e19790.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Liang XB, Luo Y, Liu XY, Lu J, Li FQ, Wang Q, et al. Electro-acupuncture improves behavior and upregulates GDNF mRNA in MFB transected rats. Neuroreport 2003, 14: 1177–1181.CrossRefPubMedGoogle Scholar
  13. 13.
    Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci 1989, 12: 366–375.CrossRefPubMedGoogle Scholar
  14. 14.
    Nambu A, Tokuno H, Takada M. Functional significance of the cortico-subthalamo-pallidal ‘hyperdirect’ pathway. Neurosci Res 2002, 43: 111–117.CrossRefPubMedGoogle Scholar
  15. 15.
    Bergman H, Wichmann T, Karmon B, DeLong MR. The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 1994, 72: 507–520.CrossRefPubMedGoogle Scholar
  16. 16.
    Moshel S, Shamir RR, Raz A, de Noriega FR, Eitan R, Bergman H, et al. Subthalamic nucleus long-range synchronization-an independent hallmark of human Parkinson’s disease. Front Syst Neurosci 2013, 7: 79–92.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Shimamoto SA, Ryapolova-Webb ES, Ostrem JL, Galifianakis NB, Miller KJ, Starr PA. Subthalamic nucleus neurons are synchronized to primary motor cortex local field potentials in Parkinson’s disease. J Neurosci 2013, 33: 7220–7233.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Baudrexel S, Witte T, Seifried C, von Wegner F, Beissner F, Klein JC, et al. Resting state fMRI reveals increased subthalamic nucleus-motor cortex connectivity in Parkinson’s disease. Neuroimage 2011, 55: 1728–1738.CrossRefPubMedGoogle Scholar
  19. 19.
    Janssen ML, Temel Y, Delaville C, Zwartjes DG, Heida T, De Deurwaerdere P, et al. Cortico-subthalamic inputs from the motor, limbic, and associative areas in normal and dopamine-depleted rats are not fully segregated. Brain Struct Funct 2016, 221: 1–13.Google Scholar
  20. 20.
    Fremeau RT, Jr., Troyer MD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, et al. The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 2001, 31: 247–260.CrossRefPubMedGoogle Scholar
  21. 21.
    Mathai A, Ma Y, Pare JF, Villalba RM, Wichmann T, Smith Y. Reduced cortical innervation of the subthalamic nucleus in MPTP-treated parkinsonian monkeys. Brain 2015, 138: 946–962.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Chu HY, McIver EL, Kovaleski RF, Atherton JF, Bevan MD. Loss of hyperdirect pathway cortico-subthalamic inputs following degeneration of midbrain dopamine neurons. Neuron 2017, 95: 1306–1318. e5.CrossRefPubMedGoogle Scholar
  23. 23.
    Wang YY, Wang Y, Jiang HF, Liu JH, Jia J, Wang K, et al. Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats. Exp Neurol 2017, 300: 135–148.CrossRefPubMedGoogle Scholar
  24. 24.
    Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, et al. Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 1998, 339: 1105–1111.CrossRefPubMedGoogle Scholar
  25. 25.
    Malkki H. Parkinson disease: deep brain stimulation might alleviate parkinsonism by reducing excessive synchronization in primary motor cortex. Nat Rev Neurol 2015, 11: 246.CrossRefPubMedGoogle Scholar
  26. 26.
    Sun M, Wang K, Yu Y, Su WT, Jiang XX, Yang J, et al. Electroacupuncture alleviates depressive-like symptoms and modulates BDNF signaling in 6-hydroxydopamine rats. Evid Based Complement Alternat Med 2016, 2016: 7842362.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Watson C, Paxinos G. The Rat Brain in Stereotaxic Coordinates 6th Edition. Academic Press, 2007: 1–463.Google Scholar
  28. 28.
    Swanger SA, Vance KM, Pare JF, Sotty F, Fog K, Smith Y, et al. NMDA receptors containing the GluN2D subunit control neuronal function in the subthalamic nucleus. J Neurosci 2015, 35: 15971–15983.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zeng WB, Jiang HF, Gang YD, Song YG, Shen ZZ, Yang H, et al. Anterograde monosynaptic transneuronal tracers derived from herpes simplex virus 1 strain H129. Mol Neurodegener 2017, 12: 38–54.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Beier KT, Steinberg EE, DeLoach KE, Xie S, Miyamichi K, Schwarz L, et al. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell 2015, 162: 622–634.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tao K, Wang B, Feng D, Zhang W, Lu F, Lai J, et al. Salidroside protects against 6-hydroxydopamine-induced cytotoxicity by attenuating ER stress. Neurosci Bull 2016, 32: 61–69.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zhao Q, Yang X, Cai D, Ye L, Hou Y, Zhang L, et al. Echinacoside protects against MPP(+)-induced neuronal apoptosis via ROS/ATF3/CHOP pathway regulation. Neurosci Bull 2016, 32: 349–362.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Limousin P, Pollak P, Benazzouz A, Hoffmann D, Le Bas JF, Broussolle E, et al. Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 1995, 345: 91–95.CrossRefPubMedGoogle Scholar
  34. 34.
    DeLong MR, Wichmann T. Circuits and circuit disorders of the basal ganglia. Arch Neurol 2007, 64: 20–24.CrossRefPubMedGoogle Scholar
  35. 35.
    Mink JW, Thach WT. Basal ganglia intrinsic circuits and their role in behavior. Curr Opin Neurobiol 1993, 3: 950–957.CrossRefPubMedGoogle Scholar
  36. 36.
    Gasnier B. The loading of neurotransmitters into synaptic vesicles. Biochimie 2000, 82: 327–337.CrossRefPubMedGoogle Scholar
  37. 37.
    Li Q, Ke Y, Chan DC, Qian ZM, Yung KK, Ko H, et al. Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex. Neuron 2012, 76: 1030–1041.CrossRefPubMedGoogle Scholar
  38. 38.
    Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K. Optical deconstruction of parkinsonian neural circuitry. Science 2009, 324: 354–359.CrossRefPubMedGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of NeurobiologyCapital Medical UniversityBeijingChina
  2. 2.Department of PhysiologyCapital Medical UniversityBeijingChina
  3. 3.Key Laboratory for Neurodegenerative DisordersThe Ministry of Education of ChinaBeijingChina
  4. 4.Beijing Institute for Brain DisordersBeijingChina

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