PUBLICATION

Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain

Authors
Bhattarai, P., Thomas, A.K., Cosacak, M.I., Papadimitriou, C., Mashkaryan, V., Zhang, Y., Kizil, C.
ID
ZDB-PUB-171121-8
Date
2017
Source
Journal of visualized experiments : JoVE   (128): (Journal)
Registered Authors
Bhattarai, Prabesh, Cosacak, Mehmet Ilyas, Kizil, Caghan, Papadimitriou, Christos
Keywords
none
MeSH Terms
  • Alzheimer Disease/chemically induced*
  • Alzheimer Disease/pathology
  • Amyloid beta-Peptides/chemical synthesis*
  • Amyloid beta-Peptides/toxicity*
  • Animals
  • Brain/drug effects*
  • Brain/pathology
  • Disease Models, Animal*
  • Nerve Degeneration/chemically induced*
  • Nerve Degeneration/pathology
  • Neurogenesis/drug effects
  • Peptide Fragments/chemical synthesis*
  • Peptide Fragments/toxicity*
  • Zebrafish
PubMed
29155703 Full text @ J. Vis. Exp.
Abstract
Alzheimer's disease (AD) is a debilitating neurodegenerative disease in which accumulation of toxic amyloid-β42 (Aβ42) peptides leads to synaptic degeneration, inflammation, neuronal death, and learning deficits. Humans cannot regenerate lost neurons in the case of AD in part due to impaired proliferative capacity of the neural stem/progenitor cells (NSPCs) and reduced neurogenesis. Therefore, efficient regenerative therapies should also enhance the proliferation and neurogenic capacity of NSPCs. Zebrafish (Danio rerio) is a regenerative organism, and we can learn the basic molecular programs with which we could design therapeutic approaches to tackle AD. For this reason, the generation of an AD-like model in zebrafish was necessary. Using our methodology, we can introduce synthetic derivatives of Aβ42 peptide with tissue penetrating capability into the adult zebrafish brain, and analyze the disease pathology and the regenerative response. The advantage over the existing methods or animal models is that zebrafish can teach us how a vertebrate brain can naturally regenerate, and thus help us to treat human neurodegenerative diseases better by targeting endogenous NSPCs. Therefore, the amyloid-toxicity model established in the adult zebrafish brain may open new avenues for research in the field of neuroscience and clinical medicine. Additionally, the simple execution of this method allows for cost-effective and efficient experimental assessment. This manuscript describes the synthesis and injection of Aβ42 peptides into zebrafish brain.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes