Long-term effects of neonatal seizures on subsequent activity-dependent NR1 and GABAA receptor α1 expressions in hippocampus of the rat

Abstract

Objective To evaluate the pathophysiological mechanism of reduced seizure threshold following neonatal seizures by measuring the expression changes in N-methyl-D-aspartate (NMDA)receptor 1(NR1)and gamma-aminobutyric acid receptor A α1(GABAARα1)immunoreactivity which are the basic functional subunit in NMDA receptor or GABAA receptor family. Methods Seizures were induced by the inhalant flurothyl in 24 neonatal rats,starting from postnatal day 6.The 24 rats were subdivided into single seizure group (seizure lasted 30 min) and recurrent seizure group (seizures were induced for 30 min/d, totally 6 d). At day 7 and day 75 after the last seizure, brain homogenates were made. The expressions of NR1 and GABAARα1 proteins in hippocampus were examined by Westem blotting analysis. Results NR1 expression did not change significantly in single seizure group and recurrent seizure group at day 75, but was enhanced significantly in recurrent seizure group at day 7(P＜0.05).Meanwhile,polypeptide levels of GABAARα1 receptor subullit in the rat hippocanlpus decreased significantly in single seizure-treated rats at day 75 and recurrent seizure-treated rats at day 7 and 75 (P＜0.05). Conclusions Recurrent or single prolonged status epilepticus in neonatal rats might cause long-term modification on NR1 and GABAARα1 expressions in hippocampus at post-seizure 7 d or in adult, with excessive activation of excitatory neuronal circuits involving both reduction of GABAARα1 receptor and/or enhancement of NR1. This phenomenon might play a key role in long-term reduction of seizure threshold induced by early life status seizures. Key words: Neonatal seizures; Seizure-induced brain injury; NR1; GABAARα1