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Open AccessArticle

Comprehensive Analysis of Neurotoxin-Induced Ablation of Dopaminergic Neurons in Zebrafish Larvae

1
Department of Biology, Faculty of Science, University of Ottawa, ON K1N 6N5, Canada
2
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(1), 1; https://doi.org/10.3390/biomedicines8010001
Received: 22 November 2019 / Revised: 24 December 2019 / Accepted: 25 December 2019 / Published: 28 December 2019
(This article belongs to the Collection Neurotoxicity: Mechanisms and Potential Therapeutic Strategies)
Neurotoxin exposure of zebrafish larvae has been used to mimic a Parkinson’s disease (PD) phenotype and to facilitate high-throughput drug screening. However, the vulnerability of zebrafish to various neurotoxins was shown to be variable. Here, we provide a direct comparison of ablative effectiveness in order to identify the optimal neurotoxin-mediated dopaminergic (DAnergic) neuronal death in larval zebrafish. Transgenic zebrafish, Tg(dat:eGFP), were exposed to different concentrations of the neurotoxins MPTP, MPP+, paraquat, 6-OHDA, and rotenone for four days, starting at three days post-fertilization. The LC50 of each respective neurotoxin concentration was determined. Confocal live imaging on Tg(dat:eGFP) showed that MPTP, MPP+, and rotenone caused comparable DAnergic cell loss in the ventral diencephalon (vDC) region while, paraquat and 6-OHDA caused fewer losses of DAnergic cells. These results were further supported by respective gene expression analyses of dat, th, and p53. Importantly, the loss of DAnergic cells from exposure to MPTP, MPP+, and rotenone impacted larval locomotor function. MPTP induced the largest motor deficit, but this was accompanied by the most severe morphological impairment. We conclude that, of the tested neurotoxins, MPP+ recapitulates a substantial degree of DAnergic ablation and slight locomotor perturbations without systemic defects indicative of a Parkinsonian phenotype. View Full-Text
Keywords: Parkinson’s disease; neurotoxins; dopaminergic neurons; ventral diencephalon; locomotor; zebrafish Parkinson’s disease; neurotoxins; dopaminergic neurons; ventral diencephalon; locomotor; zebrafish
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Kalyn, M.; Hua, K.; Mohd Noor, S.; Wong, C.E.D.; Ekker, M. Comprehensive Analysis of Neurotoxin-Induced Ablation of Dopaminergic Neurons in Zebrafish Larvae. Biomedicines 2020, 8, 1.

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