PUBLICATION
Modeling Amyloid-?42 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
-
- Amyloid beta-Peptides/chemical synthesis*
- Amyloid beta-Peptides/toxicity*
- Nerve Degeneration/chemically induced*
- Nerve Degeneration/pathology
- Alzheimer Disease/chemically induced*
- Alzheimer Disease/pathology
- Animals
- Zebrafish
- Disease Models, Animal*
- Brain/drug effects*
- Brain/pathology
- Peptide Fragments/chemical synthesis*
- Peptide Fragments/toxicity*
- Neurogenesis/drug effects
- PubMed
- 29155703 Full text @ J. Vis. Exp.
Citation
Bhattarai, P., Thomas, A.K., Cosacak, M.I., Papadimitriou, C., Mashkaryan, V., Zhang, Y., Kizil, C. (2017) Modeling Amyloid-?42 Toxicity and Neurodegeneration in Adult Zebrafish Brain. Journal of visualized experiments : JoVE. (128).
Abstract
Alzheimer's disease (AD) is a debilitating neurodegenerative disease in which accumulation of toxic amyloid-?42 (A?42) 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 A?42 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 A?42 peptides into zebrafish brain.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping