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

Autor: Taspinar N; Department of Medical Pharmacology, Faculty of Medicine, Uşak University, Uşak, Turkey., Hacimuftuoglu A; Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey., Butuner S; Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey., Togar B; Department of Medical Services and Techniques, Vocational School of Health Services, Bayburt University, Bayburt, Turkey., Arslan G; Department of Physiology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey., Taghizadehghalehjoughi A; Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey., Okkay U; Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey., Agar E; Department of Physiology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey., Stephens R Jr; Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA., Turkez H; Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey., Abd El-Aty AM; Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey.; Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Jazyk: angličtina
Zdroj: Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2021 Dec; Vol. 48 (12), pp. 1662-1673. Date of Electronic Publication: 2021 Aug 28.
DOI: 10.1111/1440-1681.13575
Abstrakt: Epilepsy 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).
(© 2021 John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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