The Study On Expression Changes Of Glutamate Transporters&Receptors In Temporal Cortex Of Epileptic Rats

Objective:Although epilepsy is one of the common neurological disorders, itspathogenesis is still unknown for us. In recent years, an imbalance betweenexcitability amino acid and inhibitory amino acid has always been studied as ankeypoint of epilepsy pathogenesis. This study was designed to observeconsecutive expression of GLAST, GLT-1, EAAC1, and GluR2in temporalcortex of epileptic rats made by Lithium-Pilocarpine combined injection. Thepurpose of this study was to make further investigation of glutamatetransporters and receptors’ effects on epilepsy development and try to provide anew method and target of epilepsy treatment.Methods:174Wistar rats were randomly divided into three groups: control group(C group), saline group (NS group), Li-Pilo epilepsy model group (EP group).Each group was divided into6subgroups：0d,1d,3d,7d,15d, and30d. Chronicepileptic rat model was made by Lithium-Pilocarpine combined injection.Behaviors changes were observed. Pathological morphological changes oftemporal cortex were studied with HE staining. Expression of GLAST、GLT-1、EAAC1、GluR2in temporal cortex were observed by immunohistochemistrymethods. Consecutive expression changes were systemically compared.Results:1. Behavior study changes:71.4%rats in EP group reach Ⅳ-Ⅴlevelseizures with a20%death rate.2. The morphological changes of temporal cortex: Degeneration andnecrosis of some neurons in temporal cortex of EP group at1d after SE, including neurons swollen, enlargement, nucleus pyknotic, cytoplasm vacuolar.Then, more neurons involved with appearance of triangle or irregular shape.Pathological changes progressed most serious during3~7d after SE.3. The immunohistochemistry study changes:(1) GLAST expression:down-regulated since3d after SE, with a peak at3~7d. Then increasedgradually, but it was still lower than normal by30d.3d,7d,15d, and30d of EPgroup had a significant difference with control group (P<0.01).(2) GLT-1expression: down-regulated since1d after SE, with a peak at1~3d. Thenincrease started by7d, and it went back to normal by30d.1d,3d,7d, and15dof EP group had a significant difference with control group (P<0.01).(3)EAAC1expression: up-regulated since1d after SE,1d and3d of EP group hasa significant difference with control group (P<0.01). With a peak at1d, then itsexpression decreased gradually and went back to normal by7d.(4) GluR2expression: GluR2expression appeared a permanent down-regulated state inEP group.1d,3d,7d,15d, and30d of EP group had a significant differencewith control group (P<0.01).Conclusion:Our study concluded:(1) Down-regulation of GLAST and GLT-1expression in latent period indicated they are possibly involved in developmentand progress of epilepsy.(2) Up-regulation of EAAC1expression wasobviously in acute period and indicated EAAC1may take participate indevelopment of epilepsy as a role of neuron protection.(3) Permanentdown-regulation of GluR2expression showed GluR2is involved indevelopment and progress of epilepsy.