Hereditary convulsions in an outbred prairie vole line

Abstract

Patients with epilepsy are significantly burdened by the disease due to long-term health risks, the severe side effect profiles of anti-epileptic drugs, and the strong possibility of pharmacoresistant refractory seizures. New animal models of epilepsy with unique characteristics promise to further research to address these ongoing problems. Here, we characterize a newly developed line of prairie voles (Microtus ochrogaster, UTol:HIC or "Toledo" line) that presents with a hereditary, adult-onset, handling-induced convulsion phenotype. Toledo voles were bred for four generations and tested to determine whether the observed phenotype was consistent with epileptic seizures. Toledo voles maintained a stable 22 % incidence of convulsions across generations, with an average age of onset of 12-16 weeks. Convulsions in Toledo voles were reliably evoked by rodent seizure screens and were phenotypically consistent with murine seizures. At the colony level, Toledo voles had a 7-fold increase in risk for sudden unexpected death from unknown causes, which parallels sudden unexpected death in epilepsy (SUDEP) in human patients. Finally, convulsions in Toledo voles were reduced or prevented by treatment with the anti-epileptic drug levetiracetam. Taken in combination, these results suggest that convulsions in Toledo voles may be epileptic seizures. The Toledo prairie vole strain may serve as a new rodent model of epilepsy in an undomesticated, outbred species.

Keywords: Animal models; Epilepsy; Neurological disorders; Seizures.

Figure 1.

The modified Racine scale for rating convulsions. Images (0-5) show examples of each Racine scale rating. No animals in this study experienced a rating of 6.

Figure 2.

The response of convulsions to levetiracetam (LVT) in N=6 experimental and N=21 control voles. (A) Diagram of the experimental timeline. Each red line represents a tossing screen. Subjects received LVT or placebo in counterbalanced order. (B) Racine scale ratings of convulsions during the pre-test, placebo, and LVT treatment phases. Symbols show individual subjects with lines connecting the time points. (C) The percent of animals that showed a reduction in convulsion severity in the placebo and LVT phases as compared to the pre-test. * p < 0.05.