Effects Of Recurrent Neonatal Seizures On Expression Of γ-aminobutyric Acid A Receptor γ2 Subunit In The Rat Brain

Objective:To investigate the effects of flurothyl-induced neonatal recurrent seizures onγ-aminobutyric acid A receptor(GABA_AR)γ2 subunit expressions in rat brain and the changes of motor ability in adult rat brain,and discuss the relationship between these alterations in developing brain and the seizure-induced brain injury.Methods:48 of 7-day-old(PT)Sprague-Dawley rats were divided randomly into two groups:the control group and the seizure group. Seizures were induced by inhalant flurothyl daily in six consecutive days. Rats were tested for motor behavior by using the open field test on PN-75d.The expression of GABA_ARγ2 subunit mRNA and protein in cerebral cortex and hippocampus were detected by immunohistochemistry and in situ hybridization method on ARS-1d and ARS-7d as well as PN-75d.Rats were also tested for motor ability by open field test on PN-75d.Results:On ARS-1d,the expressions of GABA_ARγ2 subunit protein in the frontal cortex,dentate gyrus(DG),CA1～CA4 region increased significantly in the seizure group than those in the control group(P＜0.05).On ARS-7d,the expressions of GABA_ARγ2 subunit protein in the frontal cortex and parietal cortex decreased significantly in the seizure group than those in the control group(P＜0.05),and the expressions of GABA_ARγ2 subunit protein in DG and CA1～CA2 regions increased significantly in the seizure group than those in the control group(P＜0.05).The expressions of GABA_ARγ2 subunit protein in the cortex and hippocampus increased significantly in the seizure group than those in the control group on ARS-1d(P＜0.05),and the expressions of GABA_ARγ2 subunit protein in the cortex decreased significantly in the seizure group than those in the control group on ARS-Td(P＜0.05).On PN-75d there were no differences in the expressions of GABA_ARγ2 subunit protein in the parietal lobe,DG,and CA1～CA3 region between the two groups(P＞0.05).The expressions of GABA_ARγ2 subunit protein in the frontal lobe and CA4 region decreased significantly in the seizure group than those in the control group(P＜0.05).On ARS-1d,the expressions of GABA_ARγ2 subunit mRNA in DG and CA1～CA4 region increased significantly in the seizure group than those in the control group(P＜0.05).And on ARS-7d the expressions of GABA_ARγ2 subunit mRNA in the cortex and dentate gyrus increased significantly in the seizure group than those in the control group(P＜0.05),but there were no differences in the expressions of GABA_ARγ2 subunit mRNA in hippocampal CA1～CA4(P＞0.05).On PN-75d there were also no differences in the expressions of GABA_ARγ2 subunit mRNA in the dentate gyrus and CA1～CA4(P＞0.05),but the the expressions of GABA_ARγ2 subunit mRNA in the frontal cortex decreased significantly than those in the control group(P＜0.05).On PN-75d open field test shows that motor activity of the rats in the seizure group were impaired,and the scores were significantly lower than those of the control rats(P＜0.05). There were no differences in the times to enter the neighbouring square(P＞0.05),the times to stand on the posterior limb of the rats in the seizure group were significantly less than those of the control rats(P＜0.05).Conclusions:Recurrent seizures in neonatal rats modify the expression of GABA_ARγ2 subunit in the cerebral cortex and hippocampus of rats,and cause long-term motor activity deficit.This phenomenon raised the possibility that abnormal GABA_AR expression might play an important role in short-term and long-term brain injury induced by early life recurrent seizures.