Phenotypic differences between fast and slow methionine sulfoximine-inbred mice: seizures, anxiety, and glutamine synthetase.

Arnaud Boissonnet, Tobias Hévor, Jean-François Cloix

Laboratoire de Neurobiologie, Rue de Chartres, Université d'Orléans, 45067 Orléans CEDEX 2, France.

Epilepsy research 2012 Jan

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Seizures induced by the convulsant methionine sulfoximine (MSO) resemble human "grand mal" epilepsy, and brain glutamine synthetase is inhibited. We recently selected two inbred lines of mice: sensitive to MSO (MSO-Fast) and resistant (MSO-Slow). In the present study, the selection pressure was increased and consanguinity established. To gain insight into the mechanisms of epileptogenesis, we studied the behaviour of MSO-Fast and MSO-Slow mice based on their responses to various convulsants and anticonvulsants, and also the kinetics of glutamine synthetase. The results show that increasing the number of generations of sib-crossings resulted in an increase in the differences between MSO-Fast and MSO-Slow mice. The dose-response curve of MSO-dependent seizures demonstrated that the MSO-Slow mice were highly insensitive to MSO-dependent seizures compared with MSO-Fast inbred mice that were highly sensitivity. The MSO-Slow were resistant to convulsions induced by various convulsants having different mechanisms of action, whereas those in the MSO-Fast line were more sensitive to kainic acid-induced seizures. These data, in addition to the effects of anticonvulsant, strongly suggest that glutamatergic pathways are most likely involved in MSO-dependent seizures, rather than GABAergic ones. This hypothesis is corroborated by the glutamine synthetase activity, which is more elevated in the MSO-Slow line. Behaviour tests showed that MSO-Slow were less anxious than MSO-Fast. Collectively, these results showed that glutamatergic pathways could be involved in the epileptogenic action of MSO, which may be related to the glutamate/glutamine cycle in the brain. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Citation

Arnaud Boissonnet, Tobias Hévor, Jean-François Cloix. Phenotypic differences between fast and slow methionine sulfoximine-inbred mice: seizures, anxiety, and glutamine synthetase. Epilepsy research. 2012 Jan;98(1):25-34