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Zebrafish Larval Locomotor Activity is Altered by Dimethyl Sulfoxide Under Two Different Exposure Scenarios
Citation:
Hill, B., D. Hunter, K. Jarema, K. Britton, J. Hedge, M. Lowery, J. Olin, AND S. Padilla. Zebrafish Larval Locomotor Activity is Altered by Dimethyl Sulfoxide Under Two Different Exposure Scenarios. SETAC (Society of Environmental Toxicology and Chemistry), virtual, Virtual, November 15 - 19, 2020. https://doi.org/10.23645/epacomptox.13177295
Impact/Purpose:
Poster presented at the Society of Environmental Toxicology and Chemistry (SETAC) meeting held November 2020. The U.S. Environmental Protection Agency is evaluating alternative methods to screen and prioritize chemicals for developmental neurotoxicity. Assessing larval zebrafish locomotor activity has been recognized as a higher throughput testing strategy to identify neurotoxic chemicals. There are, however, no standardized protocols for these assays, which could result in confounding variables being overlooked. These experiments were conducted to determine if dimethyl sulfoxide (DMSO), a commonly used vehicle in zebrafish screening studies affects locomotor activity, which could potentially confound study interpretation. Our results indicate that DMSO exposure can affect larval zebrafish locomotor activity at routinely used concentrations in developmental neurotoxicity assessments. Overall, these results highlight the importance of understanding the influence of experimental conditions on zebrafish larval locomotor activity that may ultimately confound the interpretation of results.
Description:
The U.S. Environmental Protection Agency is evaluating alternative methods to screen and prioritize chemicals for developmental neurotoxicity. Assessing larval zebrafish locomotor activity has been recognized as a higher throughput testing strategy to identify neurotoxic chemicals. There are, however, no standardized protocols for these assays, which could result in confounding variables being overlooked. Dimethyl sulfoxide (DMSO), a commonly used vehicle, has been reported to affect locomotor activity in larval zebrafish; however, these studies have not been conducted using many concentrations which fall within the range most often used in behavioral assessment, and results vary with experimental conditions and the type of assay. We selected a DMSO range (0.3-1% v/v DMSO; anhydrous ≥99.9% pure), representative of commonly used DMSO concentrations in zebrafish behavior studies, with narrow concentration spacing for better definition of the dose-response relationship. The influence of two different DMSO exposure scenarios on zebrafish behavior was investigated: locomotor activity was assessed in morphologically normal larvae at 144 hours post-fertilization (hpf) after either developmental (6-144 hpf) or acute (1.5 h prior to locomotor testing at 144 hours post fertilization) DMSO exposures. Results showed that locomotor activity was affected as low as 0.5% v/v DMSO for both scenarios, however more concentrations affected activity after developmental, as compared to acute, exposure to DMSO. Interestingly, DMSO exposure caused biphasic activity patterns for both exposure scenarios, but larvae exposed to DMSO during development were affected during the dark photoperiod, whereas larvae exposed acutely were only affected during the light photoperiod. Finally, DMSO produced no increases in overt toxicity (mortality and morphological changes) as compared to the DMSO-free control. These results indicate that acute and developmental DMSO exposure can affect larval zebrafish locomotor activity at routinely used concentrations in developmental neurotoxicity assessments. Overall, these results also highlight the importance of understanding the influence of experimental conditions on zebrafish larval locomotor activity that may ultimately confound the interpretation of results. This abstract may not necessarily reflect official Agency policy.
URLs/Downloads:
DOI: Zebrafish Larval Locomotor Activity is Altered by Dimethyl Sulfoxide Under Two Different Exposure Scenarios
HILL ET AL. 2020 SETAC NORTH AMERICA POSTER.PDF (PDF, NA pp, 239 KB, about PDF)