The Effects Of Neonatal Recurrent Seizures On γ-aminobutyric Acid B1 Receptor Expression In The Rat Brain

Objective: To investigate the effects of flurothyl-induced recurrent seizures in neonatal rats onγ-aminobutyric acid (GABA)B1 receptor (GABAB1R) expression in neonatal and adult rat brain, and discuss the relationship between these alterations of GABAB1R in mature brain and the changes of spatial memory and seizure susceptibility in adult rat.Methods: 48 of postnatal 7d (P7) sprague-Dawley rats were divided randomly into two groups: the control group and the seizure group. Rat pups in seizure group were induced seizures by inhalant flurothyl daily in six consecuive days. Brain tissues were sampled on 7d after the last seizure and P75 in each group. The expressions of GABAB1R mRNA and protein in cerebral cortex and hippocampus were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immuno-histochemistry method. The rats, which were sacrificed at P75, were tested for spatial memory by using the Morris water maze task during P61 to P64, and seizure threshold by intraperitoneal injection of pentylenetetrazol (PTZ) on P75.Results:①The expressions of GABAB1R are extensive in the developing and developed rat cerebral cortex and dentate gyrus(DG).②Compared with the control rats, the expressions of GABAB1R mRNA and protein in the cerebral cortex on the 7d after the last seizure and P75 decreased significantly in seizure group (P＜0.05). The expression of GABAB1R mRNA in the hippocampus and GABAB1R protein in DG on the 7d after the last seizure decreased significantly in the seizure group than those in the control group (P＜0.05), but the expression of GABAB1R were no significant differences between the two group in the hippocampus on P75 (P＞0.05).③On P64, the escape latencies in water maze of the rats in the seizure group were significantly longer than those of the control rats.④There was no difference in seizures threshold between two groups (P＝0.36).Conclusions:①The expressions of GABAB1R mRNA and protein in the cerebral cortex and hippocampus of neonatal rats with recurrent seizures decreased significantly, suggesting the change of GABAB1R is related to brain injury after neonatal recurrent seizures.②the long-term change of GABAB1R after neonatal recurrent seizures is related to the deficit of memory in adult rat caused recurrent seizures in the neonatal rats.