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The Nicotine-Evoked Locomotor Response: A Behavioral Paradigm for Toxicity Screening in Zebrafish (Danio rerio) Embryos and Eleutheroembryos Exposed to Methylmercury.

ABSTRACT: This study is an adaptation of the nicotine-evoked locomotor response (NLR) assay, which was originally utilized for phenotype-based neurotoxicity screening in zebrafish embryos. Zebrafish embryos do not exhibit spontaneous swimming until roughly 4 days post-fertilization (dpf), however, a robust swimming response can be induced as early as 36 hours post-fertilization (hpf) by means of acute nicotine exposure (30-240μM). Here, the NLR was tested as a tool for early detection of locomotor phenotypes in 36, 48 and 72 hpf mutant zebrafish embryos of the non-touch-responsive maco strain; this assay successfully discriminated mutant embryos from their non-mutant siblings. Then, methylmercury (MeHg) was used as a proof-of-concept neurotoxicant to test the effectiveness of the NLR assay as a screening tool in toxicology. The locomotor effects of MeHg were evaluated in 6 dpf wild type eleutheroembryos exposed to waterborne MeHg (0, 0.01, 0.03 and 0.1μM). Afterwards, the NLR assay was tested in 48 hpf embryos subjected to the same MeHg exposure regimes. Embryos exposed to 0.01 and 0.03μM of MeHg exhibited significant increases in locomotion in both scenarios. These findings suggest that similar locomotor phenotypes observed in free swimming fish can be detected as early as 48 hpf, when locomotion is induced with nicotine.

SUBMITTER: Mora-Zamorano FX

PROVIDER: S-EPMC4849578 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Populations of plants and animals, including humans, living in close proximity to abandoned uranium mine sites are vulnerable to uranium exposure through drainage into nearby waterways, soil accumulation, and blowing dust from surface soils. Little is known about how the environmental impact of uranium exposure alters the health of human populations in proximity to mine sites, so we used developmental zebrafish (Danio rerio) to investigate uranium toxicity. Fish are a sensitive target for modeling uranium toxicity, and previous studies report altered reproductive capacity, enhanced DNA damage, and gene expression changes in fish exposed to uranium. In our study, dechorionated zebrafish embryos were exposed to a concentration range of uranyl acetate (UA) from 0 to 3000 μg/L for body burden measurements and developmental toxicity assessments. Uranium was taken up in a concentration-dependent manner by 48 and 120 h post fertilization (hpf)-zebrafish without evidence of bioaccumulation. Exposure to UA was not associated with teratogenic outcomes or 24 hpf behavioral effects, but larvae at 120 hpf exhibited a significant hypoactive photomotor response associated with exposure to 3 μg/L UA which suggested potential neurotoxicity. To our knowledge, this is the first time that uranium has been associated with behavioral effects in an aquatic organism. These results were compared to potential metal co-contaminants using the same exposure paradigm. Similar to uranium exposure, lead, cadmium, and iron significantly altered neurobehavioral outcomes in 120-hpf zebrafish without inducing significant teratogenicity. Our study informs concerns about the potential impacts of developmental exposure to uranium on childhood neurobehavioral outcomes. This work also sets the stage for future, environmentally relevant metal mixture studies. Summary Uranium exposure to developing zebrafish causes hypoactive larval swimming behavior similar to the effect of other commonly occurring metals in uranium mine sites. This is the first time that uranium exposure has been associated with altered neurobehavioral effects in any aquatic organism.

Dataset Information

The Nicotine-Evoked Locomotor Response: A Behavioral Paradigm for Toxicity Screening in Zebrafish (Danio rerio) Embryos and Eleutheroembryos Exposed to Methylmercury.

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