The possibility that a metabolomic approach can inform about the pathophysiology of a given form of epilepsy was addressed. Using chemometric analyses of HRMAS NMR data, we compared several brain structures in three rat strains with different susceptibilities to absence epilepsy: Genetic Absence Epilepsy Rats from Strasbourg (GAERS), Non Epileptic Control rats (NEC), and Wistar rats. Two ages were investigated: 14 days postnatal (P14) before the onset of seizures and 5 month old adults with fully developed seizures (Adults). The relative concentrations of 19 metabolites were assessed using (1)H HRMAS NMR experiments. Univariate and multivariate analyses including multiblock models were used to identify the most discriminant metabolites. A strain-dependent evolution of glutamate, glutamine, scyllo-inositol, alanine, and glutathione was highlighted during cerebral maturation. In Adults, data from somatosensory and motor cortices allowed discrimination between GAERS and NEC rats with higher levels of scyllo-inositol, taurine, and phosphoethanolamine in NEC. This epileptic metabolic phenotype was in accordance with current pathophysiological hypothesis of absence epilepsy (i.e., seizure-generating and control networks) and putative resistance of NEC rats and was observed before seizure onset. This methodology could be very efficient in a clinical context.
Keywords: absence epilepsy; consensus OPLS-DA; metabolomics; multiblock model; multivariate statistical analysis; rat models.