Short-term And Long-term Effects Of Recurrent Neonatal Seizures On Expression Of GABA_A Receptor α1 And β2 Subunits In The Rat Brain

Objective:To investigate the short-term and long-term effects of flurothyl-induced neonatal recurrent seizures onγ-aminobutyric acid A receptor(GABA_AR)α1 andβ2 subunit expressions in rat brain.Methods:96 of postnatal(PN-)7d Sprague-Dawley(SD)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.The brains of rats were sampled on after-recurrent-seizure(ARS-)1d(PN-13d),ARS-7d(PN-19d)and PN-75d.The expressions of GABA_ARα1 andβ2 subunits protein in cerebral cortex and hippocampus were detected by immunohistochemistry and Western blots methods.Results:①Immunohistochemistry:On ARS-1d(PN-13d),the accumulated optical density(AOD)of GABA_ARα1 subunit immunoreactivity(IR)in the parietal cortex,dentate gyrus(DG),CA3and CA4 region increased significantly in seizure rats than those in the control rats(P＜0.05),but the AOD of GABA_ARβ2 subunit IR were similar between two groups(P＞0.05).On ARS-7d(PN-19d),the AOD of GABA_ARα1 subunit IR in the parietal cortex,DG,CA1- CA4 region and the AOD of GABA_ARβ2 subunit IR in the CA1,CA2,CA4 region increased significantly in seizure rats than those in control rats(P＜0.05), but the AOD of GABA_ARβ2 subunit IR in the thalamus decreased significantly in seizure rats than those in the control rats(P＜0.05).On PN-75d,the AOD of GABA_ARα1 subunit IR in the parietal cortex,CA1, CA2 and CA4 region decreased significantly in seizure rats than those in control rats(P＜0.05),the AOD of GABA_ARβ2 subunit IR in the thalamus and CA1-CA4 region decreased significantly in seizure rats than those in control rats(P＜0.05).②Western blots:On ARS-1d and ARS-7d,the expression of GABA_ARα1 subunit in cerebral cortex and hippicampus increased significantly in seizure rats than those in the control rats(P＜0.05).On PN-75d,the expression of GABA_ARα1 subunit in hippicampus decreased significantly in seizure rats than those in the control rats(P＜0.05).On ARS-1d and ARS-7d,the expression of GABA_ARβ2 subunit in cerebral cortex were similar between two groups(P＞0.05),but on ARS-7d,the expression of GABA_ARβ2 subunit in hippicampus increased significantly in seizure rats than those in the control rats(P＜0.05).On PN-75d,the expression of GABA_ARβ2 subunit in hippicampus decreased significantly in seizure rats than those in the control rats(P＜0.05).Conclusions:Recurrent seizures in neonatal rats modify GABA_AR receptorα1 andβ2 subunits expression in the developmental and adult rat brain.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.