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New Zebrafish Models of Neurodegeneration

  • Genetics (V Bonifati, Section Editor)
  • Published:
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Abstract

In modern biomedicine, the increasing need to develop experimental models to further our understanding of disease conditions and delineate innovative treatments has found in the zebrafish (Danio rerio) an experimental model, and indeed a valuable asset, to close the gap between in vitro and in vivo assays. Translation of ideas at a faster pace is vital in the field of neurodegeneration, with the attempt to slow or prevent the dramatic impact on the society’s welfare being an essential priority. Our research group has pioneered the use of zebrafish to contribute to the quest for faster and improved understanding and treatment of neurodegeneration in concert with, and inspired by, many others who have primed the study of the zebrafish to understand and search for a cure for disorders of the nervous system. Aware of the many advantages this vertebrate model holds, here, we present an update on the recent zebrafish models available to study neurodegeneration with the goal of stimulating further interest and increasing the number of diseases and applications for which they can be exploited. We shall do so by citing and commenting on recent breakthroughs made possible via zebrafish, highlighting their benefits for the testing of therapeutics and dissecting of disease mechanisms.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Stewart AM et al. Zebrafish models for translational neuroscience research: from tank to bedside. Trends Neurosci. 2014;37(5):264–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Rennekamp AJ, Peterson RT. 15 years of zebrafish chemical screening. Curr Opin Chem Biol. 2014;24C:58–70.

    Google Scholar 

  3. Phillips JB, Westerfield M. Zebrafish models in translational research: tipping the scales toward advancements in human health. Dis Models Mech. 2014;7(7):739–43.

    Article  Google Scholar 

  4. Schmid B, Haass C. Genomic editing opens new avenues for zebrafish as a model for neurodegeneration. J Neurochem. 2013;127(4):461–70.

    Article  CAS  PubMed  Google Scholar 

  5. Ivanes F et al. The compound BTB06584 is an IF1-dependent selective inhibitor of the mitochondrial F1 Fo-ATPase. Br J Pharmacol. 2014;171(18):4193–206.

    Article  CAS  PubMed  Google Scholar 

  6. Cunliffe VT et al. Epilepsy research methods update: understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms. Seizure. 2014;24:44–51.

    Article  PubMed  Google Scholar 

  7. Shah DI et al. Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts. Nature. 2012;491(7425):608–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Wager K, Russell C. Mitophagy and neurodegeneration: the zebrafish model system. Autophagy. 2013;9(11):1693–709.

    Article  CAS  PubMed  Google Scholar 

  9. Wager K, Mahmood F, Russell C. Modelling inborn errors of metabolism in zebrafish. J Inherit Metab Dis. 2014;37(4):483–95.

    Article  CAS  PubMed  Google Scholar 

  10. Caramillo EM et al. Modeling PTSD in the zebrafish: are we there yet? Behav Brain Res. 2015;276:151–60.

    Article  PubMed  Google Scholar 

  11. Nguyen M, Stewart AM, Kalueff AV. Aquatic blues: modeling depression and antidepressant action in zebrafish. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;55:26–39.

    Article  CAS  Google Scholar 

  12. Nasevicius A, Ekker SC. Effective targeted gene ‘knockdown’ in zebrafish. Nat Genet. 2000;26(2):216–20.

    Article  CAS  PubMed  Google Scholar 

  13. Auer TO, Del Bene F. CRISPR/Cas9 and TALEN-mediated knock-in approaches in zebrafish. Methods. 2014;69(2):142–50. Auer et al. review the use and application of genome editing approaches that are relatively novel to zebrafish.

    Article  CAS  PubMed  Google Scholar 

  14. Kasher PR et al. Impairment of the tRNA-splicing endonuclease subunit 54 (tsen54) gene causes neurological abnormalities and larval death in zebrafish models of pontocerebellar hypoplasia. Hum Mol Genet. 2011;20(8):1574–84.

    Article  CAS  PubMed  Google Scholar 

  15. Schaffer AE et al. CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell. 2014;157(3):651–63. Schaffer et al. use zebrafish to confirm CLP1 mutations as causing pontocerebellar hypoplasia.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Mahmood F et al. A zebrafish model of CLN2 disease is deficient in tripeptidyl peptidase 1 and displays progressive neurodegeneration accompanied by a reduction in proliferation. Brain. 2013;136(Pt 5):1488–507. Mahmood et al. show that locomotion assays can be used to show different movement phenotypes developing over time.

    Article  PubMed  Google Scholar 

  17. O' Donnell KC et al. Axon degeneration and PGC-1α-mediated protection in a zebrafish model of α-synuclein toxicity. Dis Models Mech. 2014;7(5):571–82. O' Donnell et al. demonstrate elegantly that PGC-1a protects against a-syn toxicity.

  18. Donnell KC, Vargas ME, Sagasti A. WldS and PGC-1α regulate mitochondrial transport and oxidation state after axonal injury. J Neurosci : Off J Soc Neurosci. 2013;33(37):14778–90. This article demonstrates the power of zebrafish for live analysis of cellular and sub-cellular phenotypes.

    Article  Google Scholar 

  19. Namavar Y et al. Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis. 2011;6:50.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Mink JW et al. Classification and natural history of the neuronal ceroid lipofuscinoses. J Child Neurol. 2013;28(9):1101–5.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Bond M et al. Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta. 2013;1832(11):1842–65.

    Article  CAS  PubMed  Google Scholar 

  22. Cerveny KL et al. The zebrafish flotte lotte mutant reveals that the local retinal environment promotes the differentiation of proliferating precursors emerging from their stem cell niche. Development. 2010;137(13):2107–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Lin MK, Farrer MJ. Genetics and genomics of Parkinson’s disease. Genome Med. 2014;6(6):48.

    Article  PubMed  Google Scholar 

  24. Ajroud-Driss S, Siddique T. Sporadic and hereditary amyotrophic lateral sclerosis (ALS). Biochim Biophys Acta. 2014;1852(4):679–84.

    Article  PubMed  Google Scholar 

  25. Vaccaro A et al. Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio. PLoS One. 2012;7(7):e42117. In this paper, methylene blue is shown to be protective for zebrafish models of ALS.

  26. Vaccaro A et al. Pharmacological reduction of ER stress protects against TDP-43 neuronal toxicity in vivo. Neurobiol Dis. 2013;55:64–75. Vaccaro et al. demonstrate mechanistic insight derived from pharmacological treatment of a zebrafish ALS model.

    Article  CAS  PubMed  Google Scholar 

  27. Jiang HQ et al. Guanabenz delays the onset of disease symptoms, extends lifespan, improves motor performance and attenuates motor neuron loss in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. Neuroscience. 2014;277:132–8.

    Article  CAS  PubMed  Google Scholar 

  28. Wang L et al. Guanabenz, which enhances the unfolded protein response, ameliorates mutant SOD1-induced amyotrophic lateral sclerosis. Neurobiol Dis. 2014;71:317–24.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Thank you to all members of the Claire Russell and Michelangelo Campanella’s research group for the on-going support. RMJ is a postdoctoral researcher funded by a research grant to CR and MC from SPARKS children’s charity.

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Conflict of Interest

Rebeca Martín-Jiménez, Michelangelo Campanella and Claire Russell declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Claire Russell.

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This article is part of the Topical Collection on Genetics

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Martín-Jiménez, R., Campanella, M. & Russell, C. New Zebrafish Models of Neurodegeneration. Curr Neurol Neurosci Rep 15, 33 (2015). https://doi.org/10.1007/s11910-015-0555-z

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  • DOI: https://doi.org/10.1007/s11910-015-0555-z

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