Environmental risk factors for multifactorial epilepsy in EL mice

Purpose: The epileptic EL mouse has been studied extensively as a model of multifactorial epilepsy. Although EL mice have a seizure occasionally durin g routine handling associated with cage changing, most studies have used vi gorous tossing or shaking procedures for seizure induction. A new seizure t esting procedure was developed that involved gentle handling-and simulated situations associated with emotional stress in rodents. This new testing pr ocedure was used to identify and characterize several environmental risk fa ctors that influence: seizure predisposition in EL mice. Methods: Ten adult EL mice were monitored for 7 days under 24-h light/dark video surveillance to assess the frequency of spontaneous seizures. The dev elopment of handling-induced seizures also was studied in EL mice, in nonep ileptic ABP and DDY mice, and in reciprocal ABP x EL F-1 hybrids from ages 30-180 days. Results: Seizure induction was necessary in EL mice, as spontaneous clinica l seizures were not observed. Handling-induced seizure susceptibility was s trongly age and ender dependent in naive EL mice (not previously handled) a nd peaked similar to 90 days, with males significantly more susceptible tha n fe-males. No seizures were induced by handling in the nonepileptic mouse strains (ABP and DDY) over the testing period. Handling and seizures at you ng ages in EL and EL x ABP F-1 hybrid mice significantly enhanced their sei zure susceptibility when they were tested again 1 month later. A significan t "Gowers effect" was seen also in EL mice. Furthermore, susceptibility was higher in ABP x EL F-1 hybrids than in their reciprocal EL x ABP F-1 hybri ds at 90-150 days. Conclusions: Seizure susceptibility in EL mice was significantly influenced by a number of environmental factors including age, gender, maternal/pater nal effects, prior handling, and seizure history. The emotional stress/fear response is the likely trigger for seizure induction in EL mice. An early life experience stress-diathesis model, similar to that proposed for major depression in humans, was applicable to the development of seizure suscepti bility in EL mice. The new seizure test will be useful for defining gen-env ironment interactions and in identifying susceptibility genes for multifact orial epilepsy.