Zebrafish as an Animal Model for Drug Discovery in Parkinson’s Disease and Other Movement Disorders: A Systematic Review

Vaz, Raquel; Outeiro, Tiago F.; Ferreira, Joaquim J.

doi:10.3389/fneur.2018.00347

Cited by 114 publications

(87 citation statements)

References 201 publications

(224 reference statements)

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“…It is reasonably wondering what's the functional significance or clinical implication for these commonly targeted PSGs. Evidence has suggested that there exist conserved molecular mechanisms between animal behaviors and human mental health disorders [54,55]. We herein deduced that the common molecular targets of selection in different animals might be associated with neuropsychiatric disorders in human.…”

Section: Common Targets In Domesticated Species Are Evolutionary Consmentioning

confidence: 85%

Genome-wide analysis reveals molecular convergence underlying domestication in 7 bird and mammals

Hou

Bai

et al. 2020

BMC Genomics

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Background: In response to ecological niche of domestication, domesticated mammals and birds developed adaptively phenotypic homoplasy in behavior modifications like fearlessness, altered sociability, exploration and cognition, which partly or indirectly result in consequences for economic productivity. Such independent adaptations provide an excellent model to investigate molecular mechanisms and patterns of evolutionary convergence driven by artificial selection. Results: First performing population genomic and brain transcriptional comparisons in 68 wild and domesticated chickens, we revealed evolutionary trajectories, genetic architectures and physiologic bases of adaptively behavioral alterations. To extensively decipher molecular convergence on behavioral changes thanks to domestication, we investigated selection signatures in hundreds of genomes and brain transcriptomes across chicken and 6 other domesticated mammals. Although no shared substitution was detected, a common enrichment of the adaptive mutations in regulatory sequences was observed, presenting significance to drive adaptations. Strong convergent pattern emerged at levels of gene, gene family, pathway and network. Genes implicated in neurotransmission, semaphorin, tectonic protein and modules regulating neuroplasticity were central focus of selection, supporting molecular repeatability of homoplastic behavior reshapes. Genes at nodal positions in trans-regulatory networks were preferably targeted. Consistent down-regulation of majority brain genes may be correlated with reduced brain size during domestication. Up-regulation of splicesome genes in chicken rather mammals highlights splicing as an efficient way to evolve since avian-specific genomic contraction of introns and intergenics. Genetic burden of domestication elicits a general hallmark. The commonly selected genes were relatively evolutionary conserved and associated with analogous neuropsychiatric disorders in human, revealing trade-off between adaption to life with human at the cost of neural changes affecting fitness in wild.

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Section: Common Targets In Domesticated Species Are Evolutionary Consmentioning

confidence: 85%

Genome-wide analysis reveals molecular convergence underlying domestication in 7 bird and mammals

Hou

Bai

et al. 2020

BMC Genomics

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“…Additionally, the dopaminergic neurons in zebrafish's posterior tuberculum (homologous to SN in human) are well characterized. When exposed to neurotoxin, zebrafish displayed alteration in locomotor activity [23]. These findings suggest that the non-mammalian species are feasible model systems to study the molecular mechanism of the disease.…”

Section: Non-mammalian Speciesmentioning

confidence: 88%

Historical Perspective: Models of Parkinson’s Disease

Chia

Tan

Chao

2020

IJMS

206

149

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Parkinson’s disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish, Caenorhabditis (C.) elegans, and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.

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“…Before investigating whether there existed difference among jawed vertebrate RAG, we selected two species that are zebrafish (Danio rerio) and mice (Mus musculus) spanning the most vertebrate evolutionary history, and they are well characterized and widely used model animals [14][15][16][17] . Our results showed that the recombination efficiency of zebrafish RAG (zRAG) was lower than that of mouse RAG (mRAG) at 37 °C.…”

mentioning

confidence: 99%

The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates

Sun

Liu

et al. 2020

Sci Rep

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The recombination activating gene (RAG or RAG1/RAG2 complex)-mediated adaptive immune system is a hallmark of jawed vertebrates. It has been reported that RAG originated in invertebrates. However, whether RAG further evolved once it arose in jawed vertebrates remains largely unknown. Here, we found that zebrafish RAG (zRAG) had a lower activity than mouse RAG (mRAG). Intriguingly, the attenuated stability of zebrafish RAG2 (zRAG2), but not zebrafish RAG1, caused the reduced V(D)J recombination efficiency compared to mRAG at 37 °C which are the body temperature of most endotherms except birds. Importantly, the lower temperature 28 °C, which is the best temperature for zebrafish growth, made the recombination efficiency of zRAG similar to that of mRAG by improving the stability of zRAG2. Consistent with the prementioned observation, the V(D)J recombination of Rag2 KI/KI mice, which zRAG2 was substituted for mRAG2, was also severely impaired. Unexpectedly, Rag2 KI/KI mice developed cachexia syndromes accompanied by premature death. Taken together, our findings illustrate that the evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates. Jawed vertebrates possess a diverse repertoire of T cell receptors (TCRs) and immunoglobulins (Igs) to specifically recognize and ultimately destroy unlimited numbers of foreign and lethal invaders or pathogens 1-3. TCRs and Igs are assembled via the recombination of variable (V), diversity (D), and joining (J) gene segments 3-5. The V(D)J recombination is a cut-and-paste reaction mediated by the RAG1/RAG2 complex (RAG) within specific genomic recombination signal sequence (RSS) sites 3,4,6. Therefore, RAG triggers the TCR-and Ig-based adaptive immune system of jawed vertebrates to defense foreign invaders 7,8. In recent decades, many scientists have carefully explored the origin of RAG 8-10. Our previous study has shown that bfRAG1L, an amphioxus RAG1-like DNA fragment, encodes a functional central domain of the vertebrate core RAG1 9. Another study found that RAG1 originated from the Transib transposase and could independently mediate V(D)J recombination 10. An interesting discovery was that of amphioxus ProtoRAG, which was demonstrated to be a cut-and-paste DNA transposon from amphioxus, placing the origination of RAG as far back as in basal chordates 8. Although the origin of RAG has been well studied, however, it has remained largely unknown whether RAG in jawed vertebrates from ectotherms to endotherms further evolved. The most evolutionarily ancient living jawed vertebrates are cartilaginous fish (e.g., horned sharks), which have been verified to have a complete set of RAGs, TCRs and Igs 2,11. When lower jawed vertebrates evolved into higher jawed vertebrates, they faced not only the transition in themselves from ectothermy to endothermy but also the transition in environment from aquatic to terrestrial. This process occurred along with numerous environmental changes associated with air,

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Zebrafish as an Animal Model for Drug Discovery in Parkinson’s Disease and Other Movement Disorders: A Systematic Review

Cited by 114 publications

References 201 publications

Genome-wide analysis reveals molecular convergence underlying domestication in 7 bird and mammals

Genome-wide analysis reveals molecular convergence underlying domestication in 7 bird and mammals

Historical Perspective: Models of Parkinson’s Disease

The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates

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