Abstracts

Rationale: Absence epilepsies are a common disease with a strong genetic aetiology. Certain environmental factors can influence absence occurrence but a complete understanding of absence precipitation is lacking. Here we investigate if lowering blood glucose increases spike-wave activity in mouse models with varying seizure susceptibility. Methods: Three mouse models were used; an absence seizure model based on the knock-in of a human GABAA?2(R43Q) mutation (DBA(R43Q)), the spike-wave discharge (SWD)-prone DBA/2J strain, and the seizure resistant C57Bl/6 strain. Electrocorticogram recordings were made to measure SWDs from mice prior to and following injection of various doses of insulin. Blood glucose was independently measured to determine the reduction in levels following insulin injection. Results: A ~45% reduction in blood glucose levels (6.7 0.3 mM to 4.0 0.4 mM, n=10, p<0.05) was sufficient to double SWD occurrence in the DBA(R43Q) model (19.9 5.9 to 50.3 5.9 SWD/h, n=10, p=0.001) and in the SWD-prone DBA/2J mouse strain(1.1 0.5 to 1.8 0.4 SWD/h, n=7, p=0.01). Larger reductions in blood glucose further increased SWDs in both these models. However, even with large reductions in blood glucose no discharges were observed in the seizure-resistant C57Bl/6 mouse strain (n=6). Injection of glucose reversed the impact of insulin on SWDs in the DBA(R43Q) model (48.5 14.2 to 20.5 9.8 SWD/h, n=5, p=0.02), supporting a reduction in blood glucose as the modulating influence.