Abstracts

Rationale: Caloric restriction (CR) involves underfeeding or undernutrition and has long been recognized as a dietary therapy that improves health and increases longevity in rodents. CR differs from fasting or malnutrition in that CR reduces total food intake without causing deficiencies of any specific nutrients, the high fat ketogenic diet (KD) is commonly used as an antiepileptic therapy in children, but little is known about the effect of CR on epilepsy. The objective of this study was to determine the influence of CR on seizure susceptibility in the EL mouse, a genetic model of multifactorial idiopathic epilepsy. Methods: The influence of CR on seizure susceptibility in male and female EL mice was determined at both juvenile (30 days) and adult (70 days) ages. The juvenile mice were separated into two groups and fed Agway lab chow either ad libitum (control, n = 18) or with a 15% CR diet (treated, n = 17). The adult EL mice were separated into three groups; control (n = 15), 15% CR (n = 8), and 30% CR (n = 4). A repetitive handling procedure was used to assess seizure susceptibility once/week for a total of ten weeks. Results: Eighty three percent of the control juvenile mice experienced seizures by week five, but seizures did not begin in the 15% CR group until week six and only 6% of these mice seized (P < 0.01). Furthermore, the incidence of mice seizing remained significantly lower in the treated group (76%) than in the control group (100%) after ten weeks of testing. A clear dosage effect was seen for the effect of CR on seizure susceptibility in the adult mice. Seizure incidence in the control, 15% CR, and 30% CR groups at week five was 88%, 50%, and 0%, respectively, and at week ten was 93%, 75%, and 50%, respectively. No adverse side effects were noticed in the behavior of the CR groups. Discussion: Mild to moderate CR delayed seizure onset and reduced seizure frequency at both juvenile and adult ages in EL mice suggesting an inhibitory effect on epileptogenesis. The antiepileptic effect of CR was greater than that found previously for the KD in EL mice. Our findings suggest that CR may be a useful dietary therapy for epilepsy in man. (Supported by the Boston College Res. Expense Fund).