| Objective:To investigate the effects of recurrent neonatal seizures on glycine receptor(GlyR)α1 andα2 subunit expressions in immature and mature rat hippocampus,and discuss the relationship between these alterations of GlyR subunits in hippocampus and the change of spatial memory in adult rat.Methods:96 of 7-day-old(PN-7d)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 spatial memory by using the Morris water maze task from PN-61d to PN-65d.The expressions of GlyRα1 andα2 subunits protein in hippocampus were detected by immunohistochemistry and Western blots methods on ARS-1d(PN-13d),ARS-7d(PN- 19d)and PN-75d.Results:On PN-64d,the escape latencies in water maze of the rats in the seizure group were significantly longer than those of the control group[(82424.3±35622.0)ms vs(40712.4±29467.6)ms,P=0.001].On PN-65d,the frequency of crossing target within 120s in water maze of the rats in the seizure group were significantly less than those of the control group[(1.2±0.9)vs(3.1±1.3),P＜0.001].In immunohistochemistry method it was found that there were no significant differences in the expressions ofα1 subunit in the hippocampus(CA1-CA4,DG)between the two groups on ARS-1d(PN-13d)and ARS-7d(PN-19d)(P＞0.05). The expressions ofα1 subunit in the dentate gyrus(DG),CA3 and CA4 regions decreased significantly in the seizure group than in the control group on PN-75d(P＜0.05),while the expressions ofα1 subunit in CA1 and CA2 regions were similar between both groups(P＞0.05).Compared to the control group,the expressions ofα2 subunit in the DG and CA4 region increased significantly in the seizure group on ARS-1d(PN-13d) and ARS-7d(PN-19d)(P＜0.05),while the expressions in CA1- CA3 regions were similar between two groups(P＞0.05).On PN-75d,there were no noticeable differences in the expressions ofα2 subunit in the hippocampus(CA1-CA4,DG)between the two groups(P＞0.05).Western blots method was used in comparing the protein expressions ofα1 andα2 subunits of the glycine receptors between the two groups in hippocampus. The expressions ofα1 subunit protein were similar on ARS-1d(PN-13d) and ARS-7d(PN-19d)(P＞0.05),then the expression ofα1 subunit protein in the seizure group significantly decreased than those in the control group(P＜0.05).The expression ofα2 subunit protein increased in the seizure group on ARS-1d(PN-13d)and ARS-7d(PN-19d)(P＞0.05),but there were no significant differences between the seizure group and the control group on PN-75d.Conclusions Recurrent seizures in neonatal rats modify the expression of glycine receptorα1 andα2 subunits in hippocampus of rats, and cause long-term cognitive deficit.This phenomenon raised the possibility that abnormal glycine receptor expression might play an important role in long-term cognitive deficit induced by early life recurrent seizures.
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