Abstract
Animal models of human neurodegenerative disease have been investigated for several decades. In recent years, zebrafish (Danio rerio) and medaka (Oryzias latipes) have become popular in pathogenic and therapeutic studies about human neurodegenerative diseases due to their small size, the optical clarity of embryos, their fast development, and their suitability to large-scale therapeutic screening. Following the emergence of a new generation of molecular biological technologies such as reverse and forward genetics, morpholino, transgenesis, and gene knockout, many human neurodegenerative disease models, such as Parkinson’s, Huntington’s, and Alzheimer’s, were constructed in zebrafish and medaka. These studies proved that zebrafish and medaka genes are functionally conserved in relation to their human homologues, so they exhibit similar neurodegenerative phenotypes to human beings. Therefore, fish are a suitable model for the investigation of pathologic mechanisms of neurodegenerative diseases and for the large-scale screening of drugs for potential therapy. In this review, we summarize the studies in modelling human neurodegenerative diseases in zebrafish and medaka in recent years.
Highlights
Neurodegenerative diseases are a major threat to human health
Neurotoxin-Induced Parkinson’s disease (PD) Models in Zebrafish and Medaka. Some neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), paraquat (1,1’-dimethyl-4,4’-bipyridinium dichloride), and rotenone are often used to selectively induce harmful effects to the dopaminergic neurons, which leads to dopaminergic neuronal loss and increases the risk of PD in model animals
Another study found that the intraperitoneal injection of MPTP in adult zebrafish caused a significant reduction of locomotory activity, accompanied by the loss of dopaminergic neurons and the over-expression of synuclein in the optic tectum [36]
Summary
With the increase in the elderly population, these age-dependent diseases are becoming increasingly prevalent [1]. Small fish such as zebrafish (Danio rerio) and medaka (Oryzias latipes) offer several advantages as model organisms for human neurodegenerative disease studies and drug discovery. Due to their relatively small size and short lifespan, they require less space and are more cost-efficient for laboratory maintenance compared with other vertebrate model organisms, such as the mouse. They have very high fecundity, and their embryos are transparent during development, which facilitates the non-invasive visualization of its development, and complex mechanisms of neurodegeneration can be analysed more rapidly than in mouse and other vertebrate animal models [7,8,9,10,11]
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