Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

Int J Mol Sci. 2020 Aug 20;21(17):5981. doi: 10.3390/ijms21175981.

Abstract

The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson's disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish's dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson's disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson's disease associated with the dopaminergic system.

Keywords: MPTP; Parkinson’s disease; dj1; dopamine; neurotransmission; paraquat; pink1; prkn; rotenone; zebrafish.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology*
  • Gene Knockdown Techniques
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / therapy
  • Oxidopamine / toxicity
  • Paraquat / toxicity
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Parkinson Disease / therapy
  • Parkinsonian Disorders / etiology
  • Parkinsonian Disorders / therapy
  • Protein Serine-Threonine Kinases / genetics
  • Rotenone / toxicity
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • Zebrafish Proteins
  • Rotenone
  • Oxidopamine
  • Pink1 protein, zebrafish
  • Protein Serine-Threonine Kinases
  • Paraquat
  • Dopamine