Differential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expression

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dc.authoridAbd El-Aty, A. M./0000-0001-6596-7907
dc.contributor.authorTaspinar, Numan
dc.contributor.authorHacimuftuoglu, Ahmet
dc.contributor.authorButuner, Selcuk
dc.contributor.authorTogar, Basak
dc.contributor.authorArslan, Gokhan
dc.contributor.authorTaghizadehghalehjoughi, Ali
dc.contributor.authorOkkay, Ufuk
dc.date.accessioned2024-10-04T18:49:30Z
dc.date.available2024-10-04T18:49:30Z
dc.date.issued2021
dc.departmentBayburt Üniversitesien_US
dc.description.abstractEpilepsy is a neurological disorder resulting from abnormal neuronal firing in the brain. Glutamate transporters and the glutamate-glutamine cycle play crucial roles in the development of seizures. In the present study, the correlation of epilepsy with glutamate transporters and enzymes was investigated. Herein, male Wistar rats were randomly allocated into four groups (six animals/group); 35 mg/kg pentylenetetrazole (PTZ) was used to induce a kindling model of epilepsy. Once the kindling model was established, animals were treated for 15 days with either valproic acid (VPA, 350 mg/kg) or ceftriaxone (CEF, 200 mg/kg) in addition to the control group receiving saline. After treatment, electrocorticography (ECoG) was performed to record the electrical activity of the cerebral cortex. The glutamate reuptake time (T-80) was also determined in situ using an in vivo voltammetry. The expression levels of glutamate transporters and enzymes in the M1 and CA3 areas of the brain were determined using a real-time polymerase chain reaction (RT-PCR). ECoG measurements showed that the mean spike number of the PTZ + VPA and PTZ + CEF groups was significantly lower (p < 0.05) than that of the PTZ group. Compared with the PTZ group, VPA or CEF treatment decreased the glutamate reuptake time (T-80). The expression levels of EAAC1, GLT-1, GLAST, glutamine synthetase (GS), and glutaminase were increased in the PTZ group. Treatment with VPA or CEF enhanced the expression levels of GLT-1, GLAST, EAAC1, and GS, whereas the glutaminase expression level was reduced. The current results suggest that VPA or CEF decreases seizure activity by increasing glutamate reuptake by upregulating GLT-1 and GLAST expression, implying a possible mechanism for treating epilepsy. Also, we have suggested a novel mechanism for the antiepileptic activity of VPA via decreasing glutaminase expression levels. To our knowledge, this is the first study to measure the glutamate reuptake time in situ during the seizure (i.e., real-time measurement).en_US
dc.description.sponsorshipAtaturk University [2015/38]; Scientific and Technological Research Council of Turkey [113S083]en_US
dc.description.sponsorshipAtaturk University, Grant/Award Number: 2015/38; Scientific and Technological Research Council of Turkey, Grant/Award Number: 113S083en_US
dc.identifier.doi10.1111/1440-1681.13575
dc.identifier.endpage1673en_US
dc.identifier.issn0305-1870
dc.identifier.issn1440-1681
dc.identifier.issue12en_US
dc.identifier.pmid34409650en_US
dc.identifier.scopus2-s2.0-85113610815en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1662en_US
dc.identifier.urihttps://doi.org/10.1111/1440-1681.13575
dc.identifier.urihttp://hdl.handle.net/20.500.12403/3186
dc.identifier.volume48en_US
dc.identifier.wosWOS:000690680400001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofClinical and Experimental Pharmacology and Physiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectelectrocorticographyen_US
dc.subjectepilepsyen_US
dc.subjectglutamate transportersen_US
dc.subjectglutaminaseen_US
dc.subjectglutamine synthetaseen_US
dc.subjectin vivo voltammetryen_US
dc.subjectpentylenetetrazoleen_US
dc.titleDifferential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expressionen_US
dc.typeArticleen_US

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