Dynamic pattern of gene expression of ZnT-1, ZnT-3 and PRG-1 in rat brain following flurothyl-induced recurrent neonatal seizures

Abstract

Zinc transporters (ZnTs) and plasticity-related genes (PRGs) both play the key roles in the formation of hippocampal mossy fiber sprouting, which is associated with cognitive deficits following developmental seizures. Here, for the first time, we report the timing of expression pattern of ZnT-1, ZnT-3 and PRG-1 in hippocampus and cerebral cortex following developmental seizures. A seizure was induced by inhalant flurothyl daily in neonatal Sprague-Dawley rats from postnatal day 6 (P6). Rats were assigned into the recurrent-seizure group (RS, seizures induced in 6 consecutive days) and the control group. At 1.5 h, 3 h, 6 h, 12 h, 24 h, 48 h, 7 d and 14 d after the last seizures, the mRNA level was detected using RT-PCR method; PRG-1 protein level was examined by Western blotting analysis. At an early period of 12 h and 48 h after the last seizures, both ZnT-1 and ZnT-3 showed significantly down-regulated mRNA level in the cerebral cortex of RS group than those at the corresponding time point in control group. In the long-term time point of 14 d after the last seizure, ZnT-3 mRNA and PRG-1 protein level in hippocampus were up-regulated while the mRNA level of ZnT-1 down-regulated; in addition, there were up-regulated level of both the mRNA and protein level of PRG-1 and down-regulated mRNA level of ZnT-3 in the cerebral cortex of RS group when compared to the control. Taken together, these dates are consistent with an important role for ZnT-1, ZnT-3 and PRG-1 in the pathophysiology of the long-term adverse effects of recurrent neonatal seizure-induced hippocampal mossy fiber sprouting and cognitive deficit.