Effects Of Progesterone On GABA Transporter1and Glutamate Transporter1Expression In The Cerebral Cortex Of Developing Rats After Recurrent Seizures

Objective:To investigate the expression of y-aminobutyric acid transport1(GAT-1) and glutamate transporter2(GLT-1) in the cerebral cortex of the developing rats following recurrent seizures and the effects of Progesterone on them, then to discuss the relationship between GAT-1together with GLT-1and immature epilepsy. On the other hand, we hope to find the anticonvulsant mechanisms of Progesterone on the developing epilepsy rats.Methods:Seventy-two of7-day-old(P7) Sprague-Dawley rats were randomly divided into three groups:the control group, the seizure group and the progesterone intervention group. Each group had24rats, which were divided into three groups randomly. Seizures were induced by inhalant flurothyl daily in six consecutive days, after that, brain tissues were sampled at different time points (ARS-1d,3d,7d) in each group after the last seizure. The expressions of GAT-1and GLT-1proteins in the cerebral cortex were detected by immunohistochemistry and Western blot methods seperately.Results:(1) immunohistochemistry results showed that:①In the control group, the GAT-1immunohistochemistry average optical density (AOD) value in cerebral cortex had no siginificant difference between ARS-1d,ARS-3d and ARS-7d; After the recurrent seizures, the GAT-1AOD value were up-regulated significantly than the control group on the three time points (P<0.01); progesterone intervention made the GAT-1AOD value down-regulated sharply than the seizure group (P<0.01), but had no significant difference between the Intra-group;②In the control group, the GLT-1AOD value in rats’cerebral cortex have no siginificant difference between each time point; After repeated seizure, the GLT-1AOD value were up-regulated clearly than the control group (P<0.01), but had no difference between three time points; progesterone intervention could up-regulated the GLT-1expression level furtherly than the seizure group in the cerebral cortex at ARS-ld,3d and7d (P<0.01),but there were no siginificantly difference between intro-group.(2) Western blot results showed that:in the control group, the GAT-1protein expression at different time point had no siginificatnly difference in rat cerebral cortex(P>0.05); After recurrent convulsions, the GAT-1expression up-regulated sharply on ARS-1d, ARS-3d and ARS-7d than the control group(P<0.01), but there were no siginificantly difference bwteen intro-group; progesterone intervention could down-regulated the GAT-1protein expression level at different time points(P<0.01), but there were no difference between intro-group;②In the control group, the GLT-1protein expression has no significant difference at different time points in rat cerebral cortex(.P>0.05);After repeatly convulsionsj, the GLT-1expression up-regulated sharply on ARS-1d, ARS-3d and ARS-7d than the control group(P<0.01), but there were no siginificantly difference bwteen intro-group; the GLT-1protein up-regulated furtherly after progesterone intervention at each time points in the cerebral cortex (P<0.01), but there were no difference between intro-group.Conclusions:(1) Neonatal recurrent seizures cause abnormal expression of GAT-1and GLT-1in the cerebral cortex, which could result in the imbalance of the involved in the pathological process of the development of convulsions, brain damage.(2) Progesterone can be involved in regulating neonatal rats with recurrent seizures caused by the imbalance in the brain cerebral cortex, GAT-1and GLT-1expression to maintain excitatory inhibitory system balance, which play an anticonvulsant brain injury.