title: Chemogenetic ablation of dopaminergic neurons leads to transient locomotor impairments in zebrafish larvae.
abstract: To determine the impact of a controlled loss of dopaminergic neurons on locomotor function, we generated transgenic zebrafish, Tg(dat:CFP-NTR), expressing a cyan fluorescent protein-nitroreductase fusion protein (CFP-NTR) under the control of dopamine transporter (dat) cis-regulatory elements. Embryonic and larval zebrafish express the transgene in several groups of dopaminergic neurons, notably in the olfactory bulb, telencephalon, diencephalon and caudal hypothalamus. Administration of the pro-drug metronidazole (Mtz) resulted in activation of caspase 3 in CFP-positive neurons and in a reduction in dat-positive cells by 5 days post-fertilization (dpf). Loss of neurons coincided with impairments in global locomotor parameters such as swimming distance, percentage of time spent moving, as well as changes in tail bend parameters such as time to maximal bend and angular velocity. Dopamine levels were transiently decreased following Mtz administration. Recovery of some of the locomotor parameters was observed by 7 dpf. However, the total numbers of dat-expressing neurons were still decreased at 7, 12, or 14 dpf, even though there was evidence for production of new dat-expressing cells. Tg(dat:CFP-NTR) zebrafish provide a model to correlate altered dopaminergic neuron numbers with locomotor function and to investigate factors influencing regeneration of dopaminergic neurons.
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, K1N-6N5, Canada.
authors.forename: Rafael
authors.initials: R
authors.lastname: Godoy
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, K1N-6N5, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Noble
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, K1N-6N5, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Yoon
authors.affiliation: Department of Neuroscience, Carleton University, Ottawa, K1S-5B6, Canada.
authors.forename: Hymie
authors.initials: H
authors.lastname: Anisman
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, K1N-6N5, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ekker
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000166:cytology / Q000254:growth & development; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics* / Q000503:physiopathology; D049452:Green Fluorescent Proteins; D006801:Humans; D007814:Larva / Q000254:growth & development; D008124:Locomotion / Q000187:drug effects*; D020267:MPTP Poisoning / Q000473:pathology; D008795:Metronidazole / Q000494:pharmacology; D009416:Nerve Regeneration; D013550:Swimming; D015027:Zebrafish
chemical_list: C485182:Cyan Fluorescent Protein; D008795:Metronidazole; D049452:Green Fluorescent Proteins
keywords: dopamine; neurodegeneration; parkinson's disease; regeneration