Neurodevelopment in seizure-prone and seizure-resistant rat strains: recognizing conflicts in management

Cytoarchitectural alterations during central nervous system (CNS) development are believed to underlie aberrations in brain morphology that lead to epilepsy. We have recently reported marked reductions in hippocampal and white matter volumes along with relative ventriculomegaly in a rat strain bred to be seizure-prone (FAST) compared to a strain bred to be seizure-resistant (SLOW) (Gilby et al., 2002, American Epilepsy Society 56th Annual Meeting). This study was designed to investigate deviations in gene expression during late-phase embryogenesis within the brains of FAST and SLOW rats. In this way, we hoped to identify molecular mechanisms operating differentially during neurodevelopment that might ultimately create the observed differences in brain morphology and/or seizure susceptibility. Using Superarray technology, we compared the expression level of 112 genes, known to play a role in neurodevelopment, within whole brains of embryonic day 21 (E21) FAST and SLOW rats. Results revealed that while most genes investigated showed near equivalent expression levels, both Apolipoprotein E (APOE) and the beta2 subunit of the voltage-gated sodium channel (SCN2beta) were significantly underexpressed in brains of the seizure-prone embryos. Currently, these transcripts have no known interactions during embryogenesis; however, they have both been independently linked to seizure disposition and/or neurodevelopmental aberrations leading to epilepsy. Thus, alterations in the timing and/or degree of expression for APOE and SCN2beta may be important to developmental cascades that ultimately give rise to the differing brain morphologies, behaviors, and/or seizure vulnerabilities that characterize these strains.