| Embryonic Exposure to Domoic Acid Increases the Susceptibility
of Zebrafish Larvae to the Chemical Convulsant Pentylenetetrazole Jessica A. Tiedeken and John S. Ramsdell Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, National Oceanic and Atmospheric Administration, National Ocean Service, Charleston, South Carolina, USA Abstract
Background: Domoic acid (DA) is a neurotoxin produced by diatoms of the genus Pseudo-nitzschia that targets the limbic system to induce tonic–clonic seizures and memory impairment. In utero DA exposure of mice leads to a reduction in seizure threshold to subsequent DA exposures in mid-postnatal life, and similar studies have shown neurotoxic effects in rats that were delayed until adolescence. Objective: We used in ovo microinjection of zebrafish (Danio rerio) to characterize the effect of embryonic exposure of DA on seizure-inducing agents later in life as an alternative species model to screen environmental contaminants that might induce a fetal-originating adult disease. Methods: Embryos were microinjected within hours of fertilization to DA concentrations ranging from 0.12 to 1.26 ng/mg egg weight. Seven days later, the larval animals were characterized for sensitivity to the chemical convulsant pentylenetetrazole (PTZ) , an agent that is well-defined in laboratory rodents and, more recently, in zebrafish. Results: In ovo DA exposure, most significantly at 0.4 ng/mg, reduces the latency time until first PTZ seizure in larval fish and increases the severity of seizures as determined by seizure stage and movement parameters. The interaction between in ovo DA exposure and PTZ caused seizure behaviors to individually asymptomatic doses of PTZ (1.0 and 1.25 mM) and DA (0.13 and 0.22 ng/mg) . Conclusion: These studies demonstrate that in ovo exposure to DA reduces the threshold to chemically induced seizures in larval fish and increases the severity of seizure behavior in a manner that is consistent with in utero studies of laboratory rodents. Key words: Danio rerio, domoic acid, EthoVision, pentylenetetrazole, seizures, zebrafish. Environ Health Perspect 115: 1547–1552 (2007) . doi:10.1289/ehp.10344 available via http://dx.doi.org/ [Online 2 August 2007]
Address correspondence to J.S. Ramsdell, Center for Coastal Environmental Health and Biomolecular Research, 219 Fort Johnson Rd., Charleston, SC 29412 USA. Telephone: (843) 762-8910. Fax: (843) 762-8700. E-mail: john.ramsdell@noaa.gov This publication does not constitute an endorsement of any commercial product or intend to be an opinion beyond scientific or other results obtained by the National Oceanic and Atmospheric Administration (NOAA) . No reference shall be made to NOAA, or this publication furnished by NOAA, to any advertising or sales promotion that would indicate or imply that NOAA recommends or endorses any proprietary product mentioned herein, or that has as its purpose an interest to cause the advertised product to be used or purchased because of this publication. The authors declare they have no competing financial interests. Received 10 April 2007 ; accepted 2 August 2007.
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