PURPOSE: Zebrafish are a vertebrate organism ideally suited to mutagenesis screening strategies. Although a genetic basis for seizure susceptibility and epilepsy is well established, no efforts have been made to study seizure resistance. Here we describe a novel strategy to isolate seizure-resistant zebrafish mutants from a large-scale mutagenesis screen. METHODS: Seizures were induced with pentylenetetrazole (PTZ). Zebrafish were analyzed between 3 and 7 days postfertilization (dpf). Genome mutations were induced in founders by using N-ethyl-nitrosourea (ENU). Seizure behavior was monitored by using a high-speed camera and quantified by locomotion-tracking software. Electrographic activity was monitored by using a field-recording electrode placed in the optic tectum of agar-immobilized zebrafish. RESULTS: Short-term PTZ exposure elicited a burst-suppression seizure pattern in 3-dpf zebrafish and more complex activity consisting of interictal- and ictal-like discharges at 7 dpf. Prolonged exposure to PTZ induced status epilepticus-like seizure activity and fatality in wild-type zebrafish larvae. With a PTZ survival assay at 6-7 dpf, we identified six zebrafish mutants in a forward-genetic screen covering nearly 2,000 F(2) families. One mutant (s334) also was shown to exhibit reduced behavioral activity on short-term PTZ exposure and an inability to generate long-duration ictal-like discharge. CONCLUSIONS: Zebrafish offers a powerful tool for the identification and study of a genetic basis for seizure resistance.
PURPOSE:Zebrafish are a vertebrate organism ideally suited to mutagenesis screening strategies. Although a genetic basis for seizure susceptibility and epilepsy is well established, no efforts have been made to study seizure resistance. Here we describe a novel strategy to isolate seizure-resistant zebrafish mutants from a large-scale mutagenesis screen. METHODS: Seizures were induced with pentylenetetrazole (PTZ). Zebrafish were analyzed between 3 and 7 days postfertilization (dpf). Genome mutations were induced in founders by using N-ethyl-nitrosourea (ENU). Seizure behavior was monitored by using a high-speed camera and quantified by locomotion-tracking software. Electrographic activity was monitored by using a field-recording electrode placed in the optic tectum of agar-immobilized zebrafish. RESULTS: Short-term PTZ exposure elicited a burst-suppression seizure pattern in 3-dpfzebrafish and more complex activity consisting of interictal- and ictal-like discharges at 7 dpf. Prolonged exposure to PTZ induced status epilepticus-like seizure activity and fatality in wild-type zebrafish larvae. With a PTZ survival assay at 6-7 dpf, we identified six zebrafish mutants in a forward-genetic screen covering nearly 2,000 F(2) families. One mutant (s334) also was shown to exhibit reduced behavioral activity on short-term PTZ exposure and an inability to generate long-duration ictal-like discharge. CONCLUSIONS:Zebrafish offers a powerful tool for the identification and study of a genetic basis for seizure resistance.
Authors: M D'Antuono; J Louvel; R Köhling; D Mattia; A Bernasconi; A Olivier; B Turak; A Devaux; R Pumain; M Avoli Journal: Brain Date: 2004-06-02 Impact factor: 13.501
Authors: Christian Lawrence; Don G Ennis; Claudia Harper; Michael L Kent; Katrina Murray; George E Sanders Journal: Comp Biochem Physiol C Toxicol Pharmacol Date: 2011-06-25 Impact factor: 3.228
Authors: J J Rahn; J E Bestman; B J Josey; E S Inks; K D Stackley; C E Rogers; C J Chou; S S L Chan Journal: Neuroscience Date: 2013-12-01 Impact factor: 3.590