DOI QR코드

DOI QR Code

Epigenetic Regulation in the Brain after Spinal Cord Injury : A Comparative Study

  • Park, Bit-Na-Ri (Department of Rehabilitation Medicine, Wonju Christian Hospital, Yonsei University Wonju College of Medicine) ;
  • Kim, Seok Won (Department of Neurosurgery, College of Medicine, Chosun University) ;
  • Cho, Sung-Rae (Department of Rehabilitation Medicine and Research Institute, Yonsei University College of Medicine) ;
  • Lee, Ji Yong (Department of Anatomy, Yonsei University Wonju College of Medicine) ;
  • Lee, Young-Hee (Department of Rehabilitation Medicine, Wonju Christian Hospital, Yonsei University Wonju College of Medicine) ;
  • Kim, Sung-Hoon (Department of Rehabilitation Medicine, Wonju Christian Hospital, Yonsei University Wonju College of Medicine)
  • Received : 2013.01.08
  • Accepted : 2013.06.19
  • Published : 2013.06.28

Abstract

Objective : After spinal cord injury (SCI), functional and structural reorganization occurs at multiple levels of brain including motor cortex. However, the underlying mechanism still remains unclear. The current study was performed to investigate the alterations in the expression of the main regulators of neuronal development, survival and death, in the brain following thoracic contusive SCI in a mouse model. Methods : Eight-week-old female imprinting control region mice (n=60; 30-35 g) were used in this study. We analyzed the expression levels of regulators such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and histone deacetylase (HDAC) 1 in the brain following thoracic contusive SCI. Results : The expression of BDNF levels were elevated significantly compared with control group at 2 weeks after injury (p<0.05). The expression of NGF levels were elevated at 2, 4 weeks compared with control group, but these difference were not significant (p>0.05). The GDNF levels were elevated at 2 week compared with control group, but these differences were not significant (p>0.05). The difference of HDAC1 levels were not significant at 2, 4 and 8 weeks compared with control group (p>0.05). Conclusion : These results demonstrate that the upregulation of BDNF may play on important role in brain reorganization after SCI.

Keywords

References

  1. Boutillier AL, Trinh E, Loeffler JP : Selective E2F-dependent gene transcription is controlled by histone deacetylase activity during neuronal apoptosis. J Neurochem 84 : 814-828, 2003 https://doi.org/10.1046/j.1471-4159.2003.01581.x
  2. Bregman BS, Goldberger ME : Infant lesion effect : II. Sparing and recovery of function after spinal cord damage in newborn and adult cats. Brain Res 285 : 119-135, 1983
  3. Bruehlmeier M, Dietz V, Leenders KL, Roelcke U, Missimer J, Curt A : How does the human brain deal with a spinal cord injury? Eur J Neurosci 10 : 3918-3922, 1998 https://doi.org/10.1046/j.1460-9568.1998.00454.x
  4. Burns SP, Golding DG, Rolle WA Jr, Graziani V, Ditunno JF Jr : Recovery of ambulation in motor-incomplete tetraplegia. Arch Phys Med Rehabil 78 : 1169-1172, 1997 https://doi.org/10.1016/S0003-9993(97)90326-9
  5. Buss A, Brook GA, Kakulas B, Martin D, Franzen R, Schoenen J, et al. : Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord. Brain 127 (Pt 1) : 34-44, 2004 https://doi.org/10.1093/brain/awh001
  6. Clark SA, Allard T, Jenkins WM, Merzenich MM : Receptive fields in the body-surface map in adult cortex defined by temporally correlated inputs. Nature 332 : 444-445, 1988 https://doi.org/10.1038/332444a0
  7. Cohen LG, Roth BJ, Wassermann EM, Topka H, Fuhr P, Schultz J, et al. : Magnetic stimulation of the human cerebral cortex, an indicator of reorganization in motor pathways in certain pathological conditions. J Clin Neurophysiol 8 : 56-65, 1991 https://doi.org/10.1097/00004691-199101000-00007
  8. Curt A, Bruehlmeier M, Leenders KL, Roelcke U, Dietz V : Differential effect of spinal cord injury and functional impairment on human brain activation. J Neurotrauma 19 : 43-51, 2002 https://doi.org/10.1089/089771502753460222
  9. Green JB, Sora E, Bialy Y, Ricamato A, Thatcher RW : Cortical sensorimotor reorganization after spinal cord injury : an electroencephalographic study. Neurology 50 : 1115-1121, 1998 https://doi.org/10.1212/WNL.50.4.1115
  10. Hajebrahimi Z, Mowla SJ, Movahedin M, Tavallaei M : Gene expression alterations of neurotrophins, their receptors and prohormone convertases in a rat model of spinal cord contusion. Neurosci Lett 441 : 261-266, 2008 https://doi.org/10.1016/j.neulet.2008.06.046
  11. Jain N, Catania KC, Kaas JH : Deactivation and reactivation of somatosensory cortex after dorsal spinal cord injury. Nature 386 : 495-498, 1997 https://doi.org/10.1038/386495a0
  12. Kim BG, Dai HN, McAtee M, Vicini S, Bregman BS : Remodeling of synaptic structures in the motor cortex following spinal cord injury. Exp Neurol 198 : 401-415, 2006 https://doi.org/10.1016/j.expneurol.2005.12.010
  13. Lee R, Kermani P, Teng KK, Hempstead BL : Regulation of cell survival by secreted proneurotrophins. Science 294 : 1945-1948, 2001 https://doi.org/10.1126/science.1065057
  14. Legube G, Trouche D : Regulating histone acetyltransferases and deacetylases. EMBO Rep 4 : 944-947, 2003 https://doi.org/10.1038/sj.embor.embor941
  15. McKinley PA, Jenkins WM, Smith JL, Merzenich MM : Age-dependent capacity for somatosensory cortex reorganization in chronic spinal cats. Brain Res 428 : 136-139, 1987
  16. Mowla SJ, Pareek S, Farhadi HF, Petrecca K, Fawcett JP, Seidah NG, et al. : Differential sorting of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons. J Neurosci 19 : 2069-2080, 1999
  17. Nudo RJ, Milliken GW, Jenkins WM, Merzenich MM : Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys. J Neurosci 16 : 785-807, 1996
  18. Pons TP, Garraghty PE, Ommaya AK, Kaas JH, Taub E, Mishkin M : Massive cortical reorganization after sensory deafferentation in adult macaques. Science 252 : 1857-1860, 1991 https://doi.org/10.1126/science.1843843
  19. Raineteau O, Schwab ME : Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci 2 : 263-273, 2001 https://doi.org/10.1038/35067570
  20. Seidah NG, Benjannet S, Pareek S, Chretien M, Murphy RA : Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases. FEBS Lett 379 : 247-250, 1996 https://doi.org/10.1016/0014-5793(95)01520-5
  21. Seidah NG, Chrétien M : Proprotein and prohormone convertases : a family of subtilases generating diverse bioactive polypeptides. Brain Res 848 : 45-62, 1999 https://doi.org/10.1016/S0006-8993(99)01909-5
  22. Waller A : Experiments on the section of glossopharyngeal and hypoglossal nerves of the frog and observations of the alternatives produced thereby in the structure of their primitive fibers. Phil Trans R Soc Lond 140 : 423, 1850 https://doi.org/10.1098/rstl.1850.0021
  23. Wrigley PJ, Gustin SM, Macey PM, Nash PG, Gandevia SC, Macefield VG, et al. : Anatomical changes in human motor cortex and motor pathways following complete thoracic spinal cord injury. Cereb Cortex 19 : 224-232, 2009 https://doi.org/10.1093/cercor/bhn072
  24. Yu SH, Cho DC, Kim KT, Nam KH, Cho HJ, Sung JK : The neuroprotective effect of treatment of valproic Acid in acute spinal cord injury. J Korean Neurosurg Soc 51 : 191-198, 2012 https://doi.org/10.3340/jkns.2012.51.4.191

Cited by

  1. Elucidation of Gene Expression Patterns in the Brain after Spinal Cord Injury vol.26, pp.7, 2013, https://doi.org/10.1177/0963689717715822