Decreased Glutamate Receptor 2 Expression and Enhanced Epileptogenesis in Immature Rat Hippocampus after Perinatal Hypoxia-Induced Seizures

Russell M. Sanchez, Sookyong Koh, Carlos Rio, Carl Wang, Ed D. Lamperti, Deepak Sharma, Gabriel Corfas, Frances E. Jensen
2001 Journal of Neuroscience  
Hypoxic encephalopathy is the most common cause of neonatal seizures and can lead to chronic epilepsy. In rats at postnatal days 10-12 (P10-12), global hypoxia induces spontaneous seizures and chronically decreases seizure threshold, thus mimicking clinical aspects of neonatal hypoxia. We have shown previously that the acute and chronic epileptogenic effects of hypoxia are age-dependent and require AMPA receptor activation. In this study, we aimed to determine whether hypoxiainduced seizures
more » ... epileptogenesis are associated with maturational and seizure-induced changes in AMPA receptor composition and function. Northern and Western blots indicated that glutamate receptor 2 (GluR2) mRNA and protein expression were significantly lower in neocortex and hippocampus at P10-12 compared with adult. After hypoxiainduced seizures at P10, GluR2 mRNA was significantly decreased within 48 hr, and GluR2 protein was significantly decreased within 96 hr. AMPA-induced Co 2ϩ uptake by neurons in hippocampal slices indicated higher expression of Ca 2ϩ -permeable AMPA receptors in immature pyramidal neurons compared with adult. In slices obtained 96 hr after hypoxia-induced seizures, AMPA-induced Co 2ϩ uptake was significantly increased compared with age-matched controls, and field recordings revealed increased tetanus-induced afterdischarges that could be kindled in the absence of NMDA receptor activation. In situ end labeling showed no acute or delayed cell death after hypoxia-induced seizures. Our results indicate that susceptibility to hypoxia-induced seizures occurs during a developmental stage in which the expression of Ca 2ϩpermeable AMPA receptors is relatively high. Furthermore, perinatal hypoxia-induced seizures induce increased expression of Ca 2ϩ -permeable AMPA receptors and an increased capacity for AMPA receptor-mediated epileptogenesis without inducing cell death.
doi:10.1523/jneurosci.21-20-08154.2001 pmid:11588188 fatcat:r3vxgms3sza5lowmsd6bess6cy