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Structural and functional regeneration after spinal cord injury in the weakly electric teleost fish, Apteronotus leptorhynchus

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Abstract

In contrast to mammals, teleost fish exhibit an enormous potential to regenerate adult spinal cord tissue after injury. However, the mechanisms mediating this ability are largely unknown. Here, we analyzed the major processes underlying structural and functional regeneration after amputation of the caudal portion of the spinal cord in Apteronotus leptorhynchus, a weakly electric teleost. After a transient wave of apoptotic cell death, cell proliferation started to increase 5 days after the lesion and persisted at high levels for at least 50 days. New cells differentiated into neurons, glia, and ependymal cells. Retrograde tract tracing revealed axonal re-growth and innervation of the regenerate. Functional regeneration was demonstrated by recovery of the amplitude of the electric organ discharge, a behavior generated by spinal motoneurons. Computer simulations indicated that the observed rates of apoptotic cell death and cell proliferation can adequately explain the re-growth of the spinal cord.

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Abbreviations

ANOVA:

Analysis of variance

BrdU:

5-bromo-2′-deoxyuridine

BSA:

Bovine serum albumine

CNS:

Central nervous system

DAPI:

4′,6-diamidino-2-phenylindoledihydrochloride

EOD:

Electric organ discharge

GFAP:

Glial fibrillary acidic protein

PB:

Phosphate buffer

PBS:

Phosphate-buffered saline

SCI:

Spinal cord injury

SD:

Standard deviation

SSC:

Saline-sodium citrate (buffer)

TBS:

Tris-buffered saline

References

  • Alvarez-Buylla A, García-Verdugo JM, Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2:287–293

    Article  PubMed  CAS  Google Scholar 

  • Bass AH (1986) Evolution of a vertebrate communication and orientation organ. In: Bullock TH, Heiligenberg W (eds) Electroreception. Wiley, New York, pp 13–70

    Google Scholar 

  • Beattie MS (2004) Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 10:580–583

    Article  PubMed  CAS  Google Scholar 

  • Beattie MS, Hermann GE, Rogers RC, Bresnahan JC (2002) Cell death in models of spinal cord injury. Prog Brain Res 137:37–47

    Article  PubMed  Google Scholar 

  • Becker CG, Becker T (2007) Zebrafish as a model system for successful spinal cord regeneration. In: Becker CG, Becker T (eds) Model organisms in spinal cord regeneration. Wiley-VCH, Weinheim, pp 289–319

    Google Scholar 

  • Becker CG, Lieberoth BC, Morellini F, Feldner J, Becker T, Schachner M (2004) L1.1 is involved in spinal cord regeneration in adult zebrafish. J Neurosci 24:7837–7842

    Article  PubMed  CAS  Google Scholar 

  • Bennett MVL (1971) Electric organs. In: Randall DJ (ed) Fish physiology: sensory systems and electric organs. Academic Press, New York, pp 347–489

    Chapter  Google Scholar 

  • Benraiss A, Arsanto JP, Coulon J, Thouveny Y (1999) Neurogenesis during caudal spinal cord regeneration in adult newts. Dev Genes Evol 209:363–369

    Article  PubMed  CAS  Google Scholar 

  • Bursch W, Paffe S, Putz B, Barthel G, Schulte-Hermann R (1990) Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats. Carcinogenesis 11:847–853

    Article  PubMed  CAS  Google Scholar 

  • Busch SA, Silver J (2007) The role of extracellular matrix in CNS regeneration. Curr Opin Neurobiol 17:120–127

    Article  PubMed  CAS  Google Scholar 

  • Chernoff EAG, Sato K, Corn A, Karcavich RE (2002) Spinal cord regeneration: intrinsic properties and emerging mechanisms. Semin Cell Dev Biol 13:361–368

    Article  PubMed  CAS  Google Scholar 

  • Chevallier S, Landry M, Nagy F, Cabelguen JM (2004) Recovery of bimodal locomotion in the spinal-transected salamander, Pleurodeles waltlii. Eur J Neurosci 20:1995–2007

    Article  PubMed  Google Scholar 

  • Clint SC, Zupanc GKH (2001) Neuronal regeneration in the cerebellum of adult teleost fish, Apteronotus leptorhynchus: guidance of migrating young cells by radial glia. Dev Brain Res 130:15–23

    Article  CAS  Google Scholar 

  • Clint SC, Zupanc GKH (2002) Up-regulation of vimentin expression during regeneration in the adult fish brain. NeuroReport 13:317–320

    Article  PubMed  CAS  Google Scholar 

  • Doyle LMF, Stafford PP, Roberts BL (2001) Recovery of locomotion correlated with axonal regeneration after a complete spinal transection in the eel. Neuroscience 107:169–179

    Article  PubMed  CAS  Google Scholar 

  • Echeverri K, Tanaka EM (2002) Ectoderm to mesoderm lineage switching during axolotl tail regeneration. Science 298:1993–1996

    Article  PubMed  CAS  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  PubMed  CAS  Google Scholar 

  • Endo T, Yoshino J, Kado K, Tochinai S (2007) Brain regeneration in anuran amphibians. Dev Growth Differ 49:121–129

    PubMed  Google Scholar 

  • Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451

    Article  PubMed  CAS  Google Scholar 

  • Ferretti P, Zhang F, O’Neill P (2003) Changes in spinal cord regenerative ability through phylogenesis and development: lessons to be learnt. Dev Dyn 226:245–256

    Article  PubMed  Google Scholar 

  • Filbin MT (2006) Recapitulate development to promote axonal regeneration: good or bad approach? Philos Trans R Soc Lond B 361:1565–1574

    Article  CAS  Google Scholar 

  • Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp Neurol 209:294–301

    Article  PubMed  CAS  Google Scholar 

  • Horky LL, Galimi F, Gage FH, Horner PJ (2006) Fate of endogenous stem/progenitor cells following spinal cord injury. J Comp Neurol 498:525–538

    Article  PubMed  Google Scholar 

  • Huard JMT, Schwob JE (1995) Cell cycle of globose basal cells in rat olfactory epithelium. Dev Dyn 203:17–26

    PubMed  CAS  Google Scholar 

  • Johansson BB (2007) Regeneration and plasticity in the brain and spinal cord. J Cereb Blood Flow Metab 27:1417–1430

    Article  PubMed  CAS  Google Scholar 

  • Klussmann S, Martin-Villalba A (2005) Molecular targets in spinal cord injury. J Mol Med 83:657–671

    Article  PubMed  CAS  Google Scholar 

  • Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4:451–464

    Article  PubMed  Google Scholar 

  • Lawson SJ, Lowrie MB (1998) The role of apoptosis and excitotoxicity in the death of spinal motoneurons and interneurons after neonatal nerve injury. Neuroscience 87:337–348

    Article  PubMed  CAS  Google Scholar 

  • Lim PAC, Tow AM (2007) Recovery and regeneration after spinal cord injury: a review and summary of recent literature. Ann Acad Med Singapore 36:49–57

    PubMed  Google Scholar 

  • Maier IC, Schwab ME (2006) Sprouting, regeneration and circuit formation in the injured spinal cord: factors and activity. Philos Trans R Soc Lond B 361:1611–1634

    Article  CAS  Google Scholar 

  • Marusich MF, Weston JA (1992) Identification of early neurogenic cells in the neural crest lineage. Dev Biol 149:295–306

    Article  PubMed  CAS  Google Scholar 

  • Mothe AJ, Tator CH (2005) Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat. Neuroscience 131:177–187

    Article  PubMed  CAS  Google Scholar 

  • Myckatyn TM, Mackinnon SE, McDonald JW (2004) Stem cell transplantation and other novel techniques for promoting recovery from spinal cord injury. Transpl Immunol 12:343–358

    Article  PubMed  CAS  Google Scholar 

  • Namihira M, Nakashima K, Taga T (2004) Developmental stage dependent regulation of DNA methylation and chromatin modification in a immature astrocyte specific gene promoter. FEBS Lett 572:184–188

    Article  PubMed  CAS  Google Scholar 

  • Profyris C, Cheema SS, Zang D, Azari MF, Boyle K, Petratos S (2004) Degenerative and regenerative mechanisms governing spinal cord injury. Neurobiol Dis 15:415–436

    Article  PubMed  Google Scholar 

  • Rakic P (2007) The radial edifice of cortical architecture: from neuronal silhouettes to genetic engineering. Brain Res Rev 55:204–219

    Article  PubMed  Google Scholar 

  • Schwab ME (2002) Repairing the injured spinal cord. Science 295:1029–1031

    Article  PubMed  CAS  Google Scholar 

  • Selinfreund RH, Barger SW, Pledger WJ, Van Eldik LJ (1991) Neurotrophic protein S100 beta stimulates glial cell proliferation. Proc Natl Acad Sci USA 88:3554–3558

    Article  PubMed  CAS  Google Scholar 

  • Siegenthaler MM, Tu MK, Keirstead HS (2007) The extent of myelin pathology differs following contusion and transection spinal cord injury. J Neurotrauma 24:1631–1646

    Article  PubMed  Google Scholar 

  • Spassky N, Merkle FT, Flames N, Tramontin AD, García-Verdugo JM, Alvarez-Buylla A (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25:10–18

    Article  PubMed  CAS  Google Scholar 

  • Stocum DL (2006) Regenerative biology and medicine. Academic Press, San Diego

    Google Scholar 

  • Stocum DL, Zupanc GKH (2008) Stretching the limits: stem cells in regeneration science. Dev Dyn 237:3648–3671

    Article  PubMed  CAS  Google Scholar 

  • Stuermer CAO, Bastmeyer M, Bähr M, Strobel G, Paschke K (1992) Trying to understand axonal regeneration in the CNS of fish. J Neurobiol 23:537–550

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Nowakowski RS, Caviness VS Jr (1993) Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse. J Neurosci 13:820–833

    PubMed  CAS  Google Scholar 

  • Takeda A, Nakano M, Goris RC, Funakoshi K (2008) Adult neurogenesis with 5-HT expression in lesioned goldfish spinal cord. Neuroscience 151:1132–1141

    Article  PubMed  CAS  Google Scholar 

  • Vessal M, Aycock A, Garton MT, Ciferri M, Darian-Smith C (2007) Adult neurogenesis in primate and rodent spinal cord: comparing a cervical dorsal rhizotomy with a dorsal column transection. Eur J Neurosci 26:2777–2794

    Article  PubMed  Google Scholar 

  • Waxman SG, Anderson MJ (1986) Regeneration of central nervous system structures: Apteronotus spinal cord as a model system. In: Bullock TH, Heiligenberg W (eds) Electroreception. Wiley, New York, pp 183–208

    Google Scholar 

  • Yamamoto S, Yamamoto N, Kitamura T, Nakamura K, Nakafuku M (2001) Proliferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord. Exp Neurol 172:115–127

    Article  PubMed  CAS  Google Scholar 

  • Yang H, Lu P, McKay HM, Bernot T, Keirstead H, Steward O, Gage FH, Edgerton VR, Tuszynski MH (2006) Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury. J Neurosci 26:2157–2166

    Article  PubMed  CAS  Google Scholar 

  • Yiu G, He Z (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7:617–627

    Article  PubMed  CAS  Google Scholar 

  • Zupanc GKH (2001) A comparative approach towards the understanding of adult neurogenesis. Brain Behav Evol 58:246–249

    Article  PubMed  CAS  Google Scholar 

  • Zupanc GKH (2006a) Neurogenesis and neuronal regeneration in the adult fish brain. J Comp Physiol A 192:649–670

    Article  CAS  Google Scholar 

  • Zupanc GKH (2006b) Adult neurogenesis and neuronal regeneration in the teleost fish brain: implication for the evolution of a primitive vertebrate trait. In: Bullock TH, Rubenstein LR (eds) The evolution of nervous systems in non-mammalian vertebrates. Academic Press, Oxford, pp 485–520

    Google Scholar 

  • Zupanc GKH (2007) Proteomics of traumatic brain injury and regeneration. Proteomics Clin Appl 1:1362–1372

    Article  CAS  Google Scholar 

  • Zupanc GKH (2008) Adult neurogenesis and neuronal regeneration in the brain of teleost fish. J Physiol (Paris) 102:357–373

    Article  Google Scholar 

  • Zupanc GKH (2009) Towards brain repair: insights from teleost fish. Semin Cell Dev Biol. doi:10.1016/j.semcdb.2008.12.001

  • Zupanc GKH, Bullock TH (2005) From electrogenesis to electroreception: an overview. In: Bullock TH, Hopkins CD, Popper AN, Fay RR (eds) Electroreception. Springer, New York, pp 5–46

    Chapter  Google Scholar 

  • Zupanc GKH, Clint SC (2003) Potential role of radial glia in adult neurogenesis of teleost fish. Glia 43:77–86

    Article  PubMed  Google Scholar 

  • Zupanc GKH, Zupanc MM (2006) New neurons for the injured brain: mechanisms of neuronal regeneration in adult teleost fish. Regen Med 1:207–216

    Article  PubMed  CAS  Google Scholar 

  • Zupanc GKH, Kompass KS, Horschke I, Ott R, Schwarz H (1998) Apoptosis after injuries in the cerebellum of adult teleost fish. Exp Neurol 152:221–230

    Article  PubMed  CAS  Google Scholar 

  • Zupanc GKH, Banks JR, Engler G, Beason RC (2003) Temperature dependence of the electric organ discharge in weakly electric fish. In: Ploger BJ, Yasukawa K (eds) Exploring animal behavior in laboratory and field. Academic Press, Amsterdam, pp 85–94

    Chapter  Google Scholar 

  • Zupanc GKH, Hinsch K, Gage FH (2005) Proliferation, migration, neuronal differentiation, and long-term survival of new cells in the adult zebrafish brain. J Comp Neurol 488:290–319

    Article  PubMed  Google Scholar 

  • Zupanc GKH, Sîrbulescu RF, Nichols A, Ilies I (2006a) Electric interactions through chirping behavior in the weakly electric fish, Apteronotus leptorhynchus. J Comp Physiol A 192:159–173

    Article  CAS  Google Scholar 

  • Zupanc MM, Wellbrock UM, Zupanc GKH (2006b) Proteome analysis identifies novel protein candidates involved in regeneration of the cerebellum of teleost fish. Proteomics 6:677–696

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study received financial support from Wilhelm Herbst Stiftung zur Förderung von Kunst und Wissenschaft, Ernst A.-C. Lange-Stiftung, Conrad Naber Stiftung, Tönjes Vagt Stiftung, and Jacobs University Bremen. We thank U. M. Wellbrock for technical assistance and C. Ubilla and M. M. Zupanc for comments on the manuscript. All experiments were performed in accordance with the relevant German law, the Deutsches Tierschutzgesetz, of 1998. All efforts were made to reduce the number of animals used and to minimize animal suffering.

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Authors and Affiliations

  1. School of Engineering and Science, Jacobs University Bremen, P.O. Box 750 561, 28725, Bremen, Germany

    Ruxandra F. Sîrbulescu & Günther K. H. Zupanc

  2. School of Humanities and Social Sciences, Jacobs University Bremen, Bremen, Germany

    Iulian Ilieş

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  1. Ruxandra F. Sîrbulescu
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  2. Iulian Ilieş
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  3. Günther K. H. Zupanc
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Correspondence to Günther K. H. Zupanc.

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Sîrbulescu, R.F., Ilieş, I. & Zupanc, G.K.H. Structural and functional regeneration after spinal cord injury in the weakly electric teleost fish, Apteronotus leptorhynchus . J Comp Physiol A 195, 699–714 (2009). https://doi.org/10.1007/s00359-009-0445-4

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