Febrile Seizure-induced Neuroexcitability in Immature Rat Hipocampus

Choi, Bong Keun; Hwang, Kyu Geun; Bae, Hae Rahn

Abstract

PURPOSE
To determine whether febrile seizure enhances neuroexcitability by altering synaptic transmission and whether febrile seizure-induced hyperexcitability leads to long-lasting neuronal death. METHODS: We investigated the expression of synaptic and postsynaptic proteins and the apoptosis of neuronal cells in rat pup hippocampus after hyperthermic seizure using immunoblotting and confocal microscopy. RESULTS: Hyperthermic seizure enhanced the long-term expressions of presynaptic proteins such as syntaxin, VAMP, SNAP-25 and nSec1, whereas that of NSF was decreased. The expressions of postsynaptic NMDA receptors 1, 2a and 2b were up-regulated. The expression of postsynaptic AMPA glutamate receptors 1 month after hyperthermic seizures altered by way of increasing the ratio of GluR1 to GluR2 and decreasing NSF-GluR2 interaction, which leads to the formation of Ca2+permeable AMPA receptors and enhanced toxicity. However, in spite of enhanced neuroexcitability, there was a transient increase of neuronal death in hipocampus one week after hyperthermic seizure, but returned to baseline one month later. CONCLUSION: These results demonstrate both presynaptic and postsynaptic forms of long-term enhancement of glutamate synaptic transmission after hyperthermic seizure and support the idea that early-life febrile seizure might have persistent effects on neuronal excitability in the hippocampus.