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Electro-acupuncture Reduces Neuronal Apoptosis Linked to Bax and Bcl-2 Expression in the Spinal Cords of Cats Subjected to Partial Dorsal Root Ganglionectomy

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Abstract

While electro-acupuncture (EA) has been well known to contribute towards neuroplasticity occurring in both the central and the peripheral nervous system after injury, the underlying mechanism remains largely unknown. This study evaluated the effects and the possible mechanism of EA on neuronal apoptosis in the spinal cords of cats subjected to the removal of L1–L5 and L7–S2 dorsal root ganglion, sparing the L6 dorsal root ganglion. EA treatment decreased the number of TUNEL-positive apoptotic cells in lamina II of the L3 and L6 cord segments at 7 and 14 days post operation (dpo). This EA-mediated neuroprotection is associated with a decrease in the number of Bax immunoreactive neurons and an increase in the number of Bcl-2 immunoreactive neurons. Furthermore, Western blot and RT-PCR analysis revealed a significant downregulation of Bax protein and its mRNA, but an upregulation of Bcl-2 in the dorsal horn of L3 and L6 cords at both 7 and 14 dpo. The present findings suggest that EA could inhibit neuronal apoptosis in dorsal root deafferentated cat spinal cords, possibly by Bax downregulation and Bcl-2 upregulation.

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References

  1. Liu CN, Chambers WW (1958) Intraspinal sprouting of dorsal root axon. Arch Neurol Psychiatry 79:46–61

    CAS  Google Scholar 

  2. Lynch G, Gall C, Rose G et al (1976) Change in the distribution of the dentate gyrus associational system following unilateral or bilateral entorhinal lesions in the adult rat. Brain Res 110:57–71

    Article  PubMed  CAS  Google Scholar 

  3. Cotman CW, Nieto-Sampedro M, Harris EW (1981) Synapse replacement in the nervous system of adult vertebrates. Physiol Rev 61:684–784

    PubMed  CAS  Google Scholar 

  4. Wu LF, Goldberger ME, Murray M (1986) Dorsal root terminal in lamina II of cat spinal cord: effects of partial deafferentation. Anat Rec 214:147A

    Google Scholar 

  5. Wu LF, Wang YM (1990) The plasticity of synaptic terminal in spinal lamina II of complete lumbosacral dorsal ganglionectomy cat: electron microscopic quantitative study. Chin J Anat 13(suppl):230A

    Google Scholar 

  6. Korsmever SJ (1992) Bcl-2 initiates a new category of oncogenes: regulators of cell death. J Blood 80:879–886

    Google Scholar 

  7. Liu XZ, Xu XM, Hu R et al (1997) Neuronal and glial apoptosis after traumatic spinal cord injury. Neuroscience 17:5395–5406

    PubMed  CAS  Google Scholar 

  8. Emery E, Aldana P, Bunge MB et al (1998) Apoptosis after traumatic human spinal cord injury. J Neurosurg 89:911–920

    Article  PubMed  CAS  Google Scholar 

  9. Nesic-Taylor O, Cittelly D, Ye Z et al (2005) Exogenous Bcl-xL fusion protein spares neurons after spinal cord injury. J Neurosci Res 795:628–637

    Article  CAS  Google Scholar 

  10. Okuno S, Saito A, Havashi T et al (2004) The c-Jun N-terminal protein kinase signaling pathway mediates Bax activation and subsequent neuronal apoptosis through interaction with Bim after transient focal cerebral ischemia. J Neurosci 24:7879–7887

    Article  PubMed  CAS  Google Scholar 

  11. Qiu J, Nesic O, Ye Z et al (2001) Bcl-xL expression after contusion to the rat spinal cord. J Neurotrauma 18:1267–1278

    Article  PubMed  CAS  Google Scholar 

  12. Cook SA, Sugden PH, Clerk A (1999) Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res 85:940–949

    PubMed  CAS  Google Scholar 

  13. Shinoura N, Yoshida Y, Asai A et al (1999) Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax. Oncogene 18:5703–5713

    Article  PubMed  CAS  Google Scholar 

  14. Lee JU, Hosotani R, Wada M et al (1999) Role of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-X) on cellular susceptibility to radiation in pancreatic cancer cells. Eur J Cancer 35:1374–1380

    Article  PubMed  CAS  Google Scholar 

  15. Luo C, Zhu C, Jiang JY et al (2001) The alterations of bcl-xL and bax mRNA expression following traumatic brain injury in rats. Chin J Traumatol 17:209–211

    CAS  Google Scholar 

  16. Motoyama N, Wang F, Roth KA et al (1995) Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. J Sci 267:1506–1510

    Article  CAS  Google Scholar 

  17. White FA, Keller-Peck CR, Knudson CM et al (1998) Widespread elimination of naturally occurring neuronal death in Bax-deficient mice. J Neurosci 18:1428–1439

    PubMed  CAS  Google Scholar 

  18. Sun W, Winseck A, Vinsant S et al (2004) Programmed cell death of adult-generated hippocampal neurons is mediated by the proapoptotic gene Bax. J Neurosci 24:11205–11213

    Article  PubMed  CAS  Google Scholar 

  19. Jin ZG, Tao ZL (1997) Study on electroacupuncture treatment of experimental spinal injury by histochemistry and immunohistochemical in cats. Chin Acupunct 8:489–492

    Google Scholar 

  20. Gao XP (1985) Acupuncture therapy of traumatic paraplegia. Chin Acupunct 5:3–4

    Google Scholar 

  21. Li GR, Ji L, Zhang S (1985) Effect of acupuncture in 124 cases of traumatic paraplegia. J Tradit Chin Med 26:34–36

    Google Scholar 

  22. Saito K, Wang C, He W (1989) Experimental and ultrastructural study of synapses in the cat spinal cord after acupuncture in zusanli. Chin J Neuroanat 5:157–164

    Google Scholar 

  23. Wu LF (1993) Effects of acupuncture on terminal of synapse in spinal cord. J WCUMS 24:117–122

    CAS  Google Scholar 

  24. Wu LF, Bao TR (1994) Electro-acupuncture stimulation enhances the neurite outgrowth promoting effect of tissue extract from Clarke’s nucleus of L6 root in cat. Chin J Neurosci 1:13–18

    Google Scholar 

  25. Dong HX, Wu LF, Bao TR (1994) The effect of acupuncture on plasticity in lamina II of cat spinal cord after partial deafferentation—a quantitative electron microscopic study. Chin J Neuroanat 10:6–11

    Google Scholar 

  26. Wang TH, Wu LF, Liao DY (2002) The effect of acupuncture on the expression of BDNF in the process of spinal plasticity. Chin J Neuroanat 18:55–58

    Google Scholar 

  27. Wang TT, Yuan Y, Kang Y et al (2005) Effects of acupuncture on the expression of glial cell line-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (FGF-2/bFGF) in the left sixth lumbar dorsal root ganglion following removal of adjacent dorsal root ganglia. Neurosci Lett 382:236–241

    Article  PubMed  CAS  Google Scholar 

  28. Wang TT, Yuan WL, Ke Q et al (2006) Effects of electro-acupuncture on the expression of c-jun and c-fos in spared dorsal root ganglion and associated spinal laminae following removal of adjacent dorsal root ganglia in cats. Neuroscience 140:1169–1176

    Article  PubMed  CAS  Google Scholar 

  29. Cheng PT, Wong MK, Chang PL (1998) A therapeutic trial of acupuncture in neurogenic bladder of spinal cord injured patients—a preliminary report. Spinal Cord 36:476–480

    Article  PubMed  CAS  Google Scholar 

  30. Pei J, Sun L, Chen R et al (2001) The effect of electroacupuncture on motor function recovery in patients with acute cerebral infarction: a randomly controlled trial. J Tradit Chin Med 21:270–272

    PubMed  CAS  Google Scholar 

  31. Wong AM, Leong CP, Su TY et al (2003) Clinical trial of acupuncture for patients with spinal cord injuries. Am J Phys Med Rehabil 82:21–27

    Article  PubMed  Google Scholar 

  32. Wang JG, Zheng QX, Zhao M (2006) Neural cell apoptosis and significant expression of Caspase-3, Fas expression after spinal cord injury in rats. Chin J Rehabil Med 21:296–300

    CAS  Google Scholar 

  33. Zhang HT, Zou XL, Song XB et al (2007) Immunohistochemical distribution of NGF, BDNF, NT-3, NT-4 in the brains of adult Rhesus monkeys. J Histochem Cytochem 55:1–19

    Article  PubMed  CAS  Google Scholar 

  34. Zhang ZY, Dang RS, Zhang CS et al (2006) Inhibitory effect of electro-acupuncture on apoptosis after spinal cord injury. Chin Nerve Regen Res 1:239–243

    CAS  Google Scholar 

  35. Cho NH, Lee JD, Cheong BS et al (2004) Acupuncture suppresses intrastriatal hemorrhage-induced apoptotic neuronal cell death in rats. Neurosci Lett 362:141–145

    Article  PubMed  CAS  Google Scholar 

  36. Zhang ZY, Cui YH, Yan ZG (2002) The effect of electric-acupuncture on apoptosis in spinal cord injury. Chin J Clin Rehabil 6:818–819

    Google Scholar 

  37. Craig RW (1995) The bcl-2 gene family. Semin Cancer Biol 6:35–43

    Article  PubMed  CAS  Google Scholar 

  38. Xiao RY, Wu LF, Li GR (1989) Influence of acupuncture on the plasticity of lamina II of cat spinal dorsal horn—a quantitative ultrastructural study. Chin J Neuroanat 5:149–155

    Google Scholar 

  39. Dong HX, Wu LF, Bao TR (1992) Influence of acupuncture on the plasticity of lamina II of cat spinal cord. Physiol Commun 3:211–214

    Google Scholar 

  40. Putcha GV, Deshmukh M, Johnson EM (1999) Bax translocation is a critical event in neuronal apoptosis: regulation by neuroprotectants, BCL-2, and Caspases. J Neurosci 19:7476–7485

    PubMed  CAS  Google Scholar 

  41. Xu J, Wu LF, Bao TR (1992) The effect of electric acupuncture on the plasticity of the synaptic terminals in Clarke’s nucleus after partial lumbosacral deafferentation of the cat spinal cord—a quantitative ultrastructural study. Chin J Neuroanat 8:47–51

    Google Scholar 

  42. Lou J, Lenle LJ, Xu F et al (1998) In vivo Bcl-2 oncogene neuronal expression in the rat spinal cord. Spine 23:517–523

    Article  PubMed  CAS  Google Scholar 

  43. Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619

    Article  PubMed  CAS  Google Scholar 

  44. Li SH, Hou TS (2001) The impact of direct-current stimulation on apoptotic adjustable gene expression of spinal cord motorneurons after sciatic nerve transection. Chin J Traumatol 17:398–401

    CAS  Google Scholar 

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Acknowledgements

We thank Dr. Kevin J. Foehrkolb and associate Professor Jiang-Fan Chen in Harvard Medical School for their very useful comments on the manuscript. A grant from the National Science Foundation (No. 30260125) and the New York-China Medical Grant (CMB00-722) supported this research.

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Correspondence to Ting-Hua Wang.

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Wei Zhao and Qi Zhao contributed equally to this work.

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Zhao, W., Zhao, Q., Liu, J. et al. Electro-acupuncture Reduces Neuronal Apoptosis Linked to Bax and Bcl-2 Expression in the Spinal Cords of Cats Subjected to Partial Dorsal Root Ganglionectomy. Neurochem Res 33, 2214–2221 (2008). https://doi.org/10.1007/s11064-008-9677-x

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  • DOI: https://doi.org/10.1007/s11064-008-9677-x

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