We investigated the relationship between brain
glycogen anabolism and
methionine sulfoximine (MSO)-induced
seizures in two inbred mouse strains that presented differential susceptibility to the
convulsant. CBA/J was considered a MSO-high-reactive strain and C57BL/6J a MSO-low-reactive strain. Accordingly, the dose of MSO needed to induce
seizures in CBA/J mice is lower than that in C57BL/6J mice, and CBA/J mice which had
seizures, died during the first convulsion. In addition, the time--course of the MSO effect is faster in CBA/J mice than that in C57BL/6J mice. Analyses were performed in C57BL/6J and CBA/J mice after administration of 75 (subconvulsive dose) and 40 mg/kg of MSO (subconvulsive dose, not lethal dose), respectively. In the preconvulsive period, MSO induced an increase in the brain
glycogen content of C57BL/6J mice only. Twenty-four hours after MSO administration, the brain
glycogen content increased in both strains. The activity and expression of
fructose-1,6-bisphosphatase, the last key
enzyme of the gluconeogenic pathway, were increased in MSO-treated C57BL/6J mice as compared to control mice, at all experimental time points, whereas they were increased in CBA/J mice only 24 h after MSO administration. These latter results correspond to CBA/J mice that did not have
seizures. Interestingly, the differences observed in vivo were consistent with results in primary cultured astrocytes from the two strains. This data suggests that the metabolism impairment, which was not a consequence of
seizures, could be related to the difference in seizure susceptibility between the two strains, depending on their genetic background.