Embryonic exposure to domoic Acid increases the susceptibility of zebrafish larvae to the chemical convulsant pentylenetetrazole.
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).


CONCLUSIONS
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.
Tiedeken
Jessica A
JA
Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, National Oceanic and Atmospheric Administration, National Ocean Service, Charleston, South Carolina 29412, USA.
Ramsdell
John S
JS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003292:Convulsants / Q000008:administration & dosage / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D005260:Female; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008297:Male; D008845:Microinjections; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage* / Q000633:toxicity; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced*; D013550:Swimming; D015027:Zebrafish / Q000254:growth & development* / Q000502:physiology
D003292:Convulsants; D009467:Neuromuscular Depolarizing Agents; C012301:domoic acid; D007608:Kainic Acid; D010433:Pentylenetetrazole