Abstracts

RATIONALE:High affinity, GABA plasma membrane transporters (GATs) influence the synaptic availability of GABA, the main inhibitory neurotransmitter in the brain. Recent studies suggest a crucial role for GATs in maintaining levels of synaptic GABA in normal as well as abnormal (i.e., epileptic) adult brain. However, the role of GATs during development and specifically changes in their expression in response to developmental seizures is unknown. METHODS: The present study examined GAT-1 immunolabeling in infant rats subject to two types of developmental seizures, those induced by corticotropin releasing hormone (CRH), and those resulting from hyperthermia (a model of prolonged febrile seizures). Sections of the forebrain from 11 day old rats with CRH-induced seizures or hyperthermia-induced seizures were immunolabeled with antibodies to GAT-1. The number of cells with GAT-1 immunoreactivity(ir) was counted in several brain regions. RESULTS: The number of GAT-1 ir neurons was increased in several forebrain regions 24 hr after induction of seizures by CRH as compared to the control group.Increased numbers of GAT-1 ir somata were found in the hippocampal formation, including hilus and CA1, and in the neocortex, piriform cortex and amygdala. In contrast, hyperthermia-induced seizures did not cause significant changes in the number of GAT-1 ir somata in any region analyzed. CONCLUSIONS: The number of GAT-1 ir somata is increased following CRH-induced seizures, but is not changed in rats with hyperthermia-induced seizures. This indicates that GATs may play a role in maintaining synaptic GABA levels in the immature brain,as has been established for the adult.The specificity of GAT upregulation for the CRH model may reflect a difference in the duration of seizures between the two models. [Supported by UC Biotechnology Research and Education Program (98-02) and NIH grants NS-35439 and NS 38331]