Skip to main content
Log in

Absence of gliosis in a teleost model of spinal cord regeneration

  • Original Paper
  • Published:
Journal of Comparative Physiology A Aims and scope Submit manuscript

Abstract

Among the cellular processes that follow injury to the central nervous system, glial scar formation is thought to be one of the major factors that prevent regeneration. In regeneration-competent organisms, glial scar formation has been a matter of controversy. We addressed this issue by examining the glial population after spinal cord injury in a model of regeneration competency, the knifefish Apteronotus leptorhynchus. Analysis of spinal cord sections immunostained against the glial markers glial fibrillary acidic protein, vimentin, or chondroitin sulfate proteoglycan failed to produce any evidence for the formation of a glial scar in the area of the lesion at post-injury survival times ranging from 5 to 185 days. This result was independent of the lesion paradigm applied—amputation of the caudal part of the spinal cord or hemisection lesioning—and similar after examination of transverse and longitudinal sections. We hypothesize that the well-developed network of radial glia in both the intact and the injured spinal cord provides a support system for regeneration of tissue lost to injury. This glial network is likely also involved in the generation of new cells, as indicated by the large subset of glial fibrillary acidic protein-labeled glia that express the stem cell marker Sox2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

References

  • Baumgart EV, Barbosa JS, Bally-Cuif L, Götz M, Ninkovic J (2012) Stab wound injury of the zebrafish telencephalon: a model for comparative analysis of reactive gliosis. Glia 60:343–357

    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 T, Wullimann MF, Becker CG, Bernhardt RR, Schachner M (1997) Axonal regrowth after spinal cord transection in adult zebrafish. J Comp Neurol 377:577–595

    Article  CAS  PubMed  Google Scholar 

  • Bernstein JJ, Bernstein ME (1969) Ultrastructure of normal regeneration and loss of regenerative capacity following teflon blockage in goldfish spinal cord. Exp Neurol 24:538–557

    Article  CAS  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 

  • Cregg JM, DePaul MA, Filous AR, Lang BT, Tran A, Silver J (2014) Functional regeneration beyond the glial scar. Exp Neurol 253:197–207

    Article  PubMed  Google Scholar 

  • Diaz Quiroz JF, Echeverri K (2013) Spinal cord regeneration: where fish, frogs and salamanders lead the way, can we follow? Biochem J 451:353–364

    Article  CAS  PubMed  Google Scholar 

  • Dusart I, Schwab ME (1994) Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci 6:712–724

    Article  CAS  PubMed  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  CAS  PubMed  PubMed Central  Google Scholar 

  • Fitch MT, Doller C, Combs CK, Landreth GE, Silver J (1999) Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after central nervous system trauma. J Neurosci 19:8182–8198

    CAS  PubMed  Google Scholar 

  • Goldshmit Y, Sztal TE, Jusuf PR, Hall TE, Nguyen-Chi M, Currie PD (2012) Fgf-dependent glial cell bridges facilitate spinal cord regeneration in zebrafish. J Neurosci 32:7477–7492

    Article  CAS  PubMed  Google Scholar 

  • Horn KP, Busch SA, Hawthorne AL, van Rooijen N, Silver J (2008) Another barrier to regeneration in the central nervous system: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J Neurosci 28:9330–9341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hui SP, Dutta A, Ghosh S (2010) Cellular response after crush injury in adult zebrafish spinal cord. Dev Dyn 239:2962–2979

    Article  PubMed  Google Scholar 

  • Kálmán M, Somiya H, Lazarevic L, Milosevic I, Ari C, Majorossy K (2013) Absence of post-lesion reactive gliosis in elasmobranchs and turtles and its bearing on the evolution of astroglia. J Exp Zool B 320:351–367

    Article  Google Scholar 

  • Kishimoto N, Shimizu K, Sawamoto K (2012) Neuronal regeneration in a zebrafish model of adult brain injury. Dis Model Mech 5:200–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kroehne V, Freudenreich D, Hans S, Kaslin J, Brand M (2011) Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors. Development 138:4831–4841

    Article  CAS  PubMed  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 

  • Lee-Liu D, Edwards-Faret G, Tapia VS, Larraín J (2013) Spinal cord regeneration: lessons for mammals from non-mammalian vertebrates. Genesis 51:529–544

    Article  PubMed  Google Scholar 

  • März M, Schmidt R, Rastegar S, Strähle U (2011) Regenerative response following stab injury in the adult zebrafish telencephalon. Dev Dyn 240:2221–2231

    Article  PubMed  Google Scholar 

  • Nona SN, Stafford CA (1995) Glial repair at the lesion site in regenerating goldfish spinal cord: an immunohistochemical study using species-specific antibodies. J Neurosci Res 42:350–356

    Article  CAS  PubMed  Google Scholar 

  • O’Hara CM, Egar MW, Chernoff EAG (1992) Reorganization of the ependyma during axolotl spinal cord regeneration: changes in intermediate filament and fibronectin expression. Dev Dyn 193:103–115

    Article  PubMed  Google Scholar 

  • Reimer MM, Sörensen I, Kuscha V, Frank RE, Liu C, Becker CG, Becker T (2008) Motor neuron regeneration in adult zebrafish. J Neurosci 28:8510–8516

    Article  CAS  PubMed  Google Scholar 

  • Rolls A, Shechter R, Schwartz M (2009) The bright side of the glial scar in central nervous system repair. Nat Rev Neurosci 10:235–241

    Article  CAS  PubMed  Google Scholar 

  • Sîrbulescu RF, Zupanc GKH (2011) Spinal cord repair in regeneration-competent vertebrates: adult teleost fish as a model system. Brain Res Rev 67:73–93

    Article  PubMed  Google Scholar 

  • Sîrbulescu RF, Zupanc GKH (2013) Neuronal regeneration. In: Evans DH, Claiborne JB, Currie S (eds) The physiology of fishes. CRC Press, Boca Raton, pp 405–441

    Google Scholar 

  • Sîrbulescu RF, Ilieş I, Zupanc GKH (2009) Structural and functional regeneration after spinal cord injury in the weakly electric teleost fish, Apteronotus leptorhynchus. J Comp Physiol A 195:699–714

    Article  Google Scholar 

  • Sîrbulescu RF, Ilieş I, Zupanc GKH (2014) Quantitative analysis reveals dominance of gliogenesis over neurogenesis in an adult brainstem oscillator. Dev Neurobiol 74:934–952

    Article  PubMed  Google Scholar 

  • Sîrbulescu RF, Ilieş I, Vitalo AG, Trull K, Zhu J, Traniello IM, Zupanc GKH (2015) Adult stem cells in the knifefish cerebellum. Dev Neurobiol 75:39–65

    Article  PubMed  Google Scholar 

  • Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35

    Article  PubMed  PubMed Central  Google Scholar 

  • Takeda A, Goris RC, Funakoshi K (2007) Regeneration of descending projections to the spinal motor neurons after spinal hemisection in the goldfish. Brain Res 1155:17–23

    Article  CAS  PubMed  Google Scholar 

  • Takeda A, Atobe Y, Kadota T, Goris RC, Funakoshi K (2015) Axonal regeneration through the fibrous scar in lesioned goldfish spinal cord. Neuroscience 284:134–152

    Article  CAS  PubMed  Google Scholar 

  • Traniello IM, Sîrbulescu RF, Ilieş I, Zupanc GKH (2014) Age-related changes in stem cell dynamics, neurogenesis, apoptosis, and gliosis in the adult brain: a novel teleost fish model of negligible senescence. Dev Neurobiol 74:514–530

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan YM, He C (2013) The glial scar in spinal cord injury and repair. Neurosci Bull 29:421–435

    Article  PubMed  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, Sîrbulescu RF (2013) Teleost fish as a model system to study successful regeneration of the central nervous system. Curr Top Microbiol Immunol 367:193–233

    CAS  PubMed  Google Scholar 

  • Zupanc GKH, Sîrbulescu RF, Ilieş I (2012) Radial glia in the cerebellum of adult teleost fish: implications for the guidance of migrating new neurons. Neuroscience 210:416–430

    Article  CAS  PubMed  Google Scholar 

  • Zupanc GKH, Ilieş I, Sîrbulescu RF, Zupanc MM (2014) Large-scale identification of proteins involved in the development of a sexually dimorphic behavior. J Neurophysiol 111:1646–1654

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding for this investigation was provided by Northeastern University to Günther K.H. Zupanc, and National Science Foundation Grant No. 1538505 awarded to Günther K.H. Zupanc and Rifat Sipahi. All animal experiments were approved by the Institutional Animal Care and Use Committee of Northeastern University. All efforts were made to reduce the number of animals used and to minimize suffering.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Günther K. H. Zupanc.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vitalo, A.G., Sîrbulescu, R.F., Ilieş, I. et al. Absence of gliosis in a teleost model of spinal cord regeneration. J Comp Physiol A 202, 445–456 (2016). https://doi.org/10.1007/s00359-016-1089-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00359-016-1089-9

Keywords

Navigation