Dynamic Pattern of Gene Expression of ZnT-4, Caspase-3, LC3, and PRG-3 in Rat Cerebral Cortex Following Flurothyl-Induced Recurrent Neonatal Seizures

Abstract

Zinc transporters, plasticity-related genes, and autophagic/apoptotic pathway both are associated with developmental seizure-induced brain excitotoxicity. Here, for the first time, we report the timing of expression pattern of zinc transporter 4 (ZnT-4), plasticity-related gene 3 (PRG-3), specific marker of autophagic vacuoles (LC3), and apoptotic marker caspase-3 in cerebral cortex following neonatal seizures. A seizure was induced by inhalant flurothyl daily in neonatal Sprague-Dawley rats from postnatal day6 (P6). Rats were assigned into the recurrent-seizure group (RS, seizures induced in six consecutive days) and the control group. At 1.5h, 3h, 6h, 12h, 24h, 48h, 7days, and 14days after the last seizure, the mRNA level of the four genes in cerebral cortex was detected using RT-PCR method. At an early period 6h or 12h after the last seizures, both ZnT-4 and LC3 showed significantly up-regulated mRNA level while PRG-3 showed significantly down-regulated mRNA level at 12h in cerebral cortex of RS group than those at the corresponding time point in control group. In the long-term time point of 7days after the last seizure, the mRNA level of caspase-3 down-regulated; meanwhile, there was up-regulated mRNA level of LC-3 in RS group when compared to the control rats. This is the first report investigating the gene expression pattern of ZnT-4, PRG-3, LC-3, and caspase-3 in the developing brain. The results suggest that the disturbed expression pattern of the four genes might play a role in the pathophysiology of recurrent neonatal seizure-induced acute and long-term brain damage.