Abstracts

Cortical dysplasia (CD) is a frequent pathology in infants and children with intractable epilepsy. Molecular characterizations of pediatric dysplastic cortex have previously revealed alterations in the subunit proteins of the N-methyl-D-aspartate (NMDA) receptor. The purpose of the study was to determine if and when the dysplastic cortex of postnatal rat pups showed altered NMDA subunit expressions compared to age matched controls. Dams were irradiated with 145 Rads (cGy) at embryonic day 17, and their offspring were studied at 24-hour intervals, postnatal ages zero through six. Cresyl violet staining allowed for dysplasia confirmation, and provided the imaging necessary for obtaining neuronal lengths and diameters from pyramidal neurons in Layer III of the cortex. The expression levels of NMDA receptor subunits NR1 and NR2B were determined using Western blotting. Statistical comparisons were made between control and irradiated age matched pups and within treatment groups between adjacent ages. Cresyl violet staining showed that all histologically examined tissue from irradiated pups was dysplastic. For NR1 and NR2B expression, there was a significant difference across ages within control and irradiated groups, but not between age-matched control and irradiated groups. In Layer III of the cortex, averaged lengths and diameters from pyramidal neurons correlated significantly across ages within control ([italic]p[/italic] = 0.002) and irradiated ([italic]p[/italic] = 0.001). Additionally, the correlation between control and irradiated age-matched samples was more significant for neuronal length ([italic]p[/italic] = 0.002) than for neuronal diameter ([italic]p[/italic] = 0.065). In this study, we used a well-known model of cortical dysplasia to determine the earliest postnatal NR1 and NR2B protein subunit expression changes. NR1 and NR2B subunits appear to be developmentally regulated at these young ages. Though expression differences between age-matched control and irradiated samples are not significant, it is possible that these expression differences will be significant at later ages when these animals are known be susceptible to seizure activity (Kondo et al., 2001). Despite the fact that all histologically examined tissue showed characteristics of cortical dysplasia, neuronal growth and NMDA subunit expression was not significantly different between control and irradiated groups during postnatal days zero through six. These young pups may not have yet developed axonal and dendritic growth sufficient for synaptic formations to allow feedforward excitation and feedback inhibition.
Kondo, S., et al. (2001). [underline]Epilepsia[/underline] (10): 1221-7. (Supported by National Institutes of Health, 5 R01 NS41375-03, and the Children[apos]s Research Center of Michigan at Children[apos]s Hospital of Michigan.)