Low glycaemic index diet reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy

摘要

Purpose: Clinical evidence suggests that low glycaemic index diets are effective at reducing seizure frequency potentially through the stabilization of blood glucose levels. Here we investigate if diets containing carbohydrates with varying glycaemic index (GI) can modulate seizure susceptibility in a mouse model of generalized epilepsy. Methods: Electrocortical recordings were made from mice harboring the GABAAγ2 (R43Q) epilepsy mutation after three weeks on a low-or high-GI diet. Standard rodent diet was used as a control. Occurrence and durations of spike-wave-discharges (SWDs) were measured. An insulin injection was used to reduce blood glucose to levels known to precipitate SWDs in the GABAAγ2 (R43Q) mouse on the low and high-GI diets. Key findings: SWD occurrence was reduced by approximately 35% in mice on the low-GI compared to high-GI diet. SWD occurrence was not different between high-GI diet and a standard diet suggesting that low-GI diet is protective. Weight gain of mice for all diet groups was identical suggesting that they were equally well tolerated. Under low blood glucose conditions SWD occurrence increased in the low and high-GI diets. Importantly, under low glucose conditions the low-GI diet no longer conferred protection against SWDs. Significance: SWDs were reduced in mice on a low GI-diet suggesting it may be an effective and well tolerated therapy for generalized epilepsy. The lack of effect of low-GI diet when glucose levels are reduced suggests that seizure protection in the GABAAγ2 (R43Q) mouse model may be due to the diets ability to stabilize blood glucose levels.