Epileptogenic effects of G protein-coupled estrogen receptor 1 in the rat pentylenetetrazole kindling model of epilepsy

BackgroundG protein-coupled estrogen receptor 1 (GPER-1) has been demonstrated in several parts of the brain and may play an important role in estrogen downstream signaling pathway. However, the effects of this receptor on epileptic seizure are not clearly known. Therefore, the effects of GPER-1 agonist, G-1, GPER-1 antagonist, G-15 and the main estrogenic hormone, 17β-estradiol were investigated on seizures and brain tissue oxidative damages induced by pentylenetetrazole (PTZ) in rats.MethodsIn this study, 30 adult male Wistar albino rats were used. Due to intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) which was repeated 12 times every 48 h, chemical kindling occurred and kindling seizure was recorded for 30 min. The rats were injected with 17β-estradiol (5 μg/kg, ip) or G-1 (5 μg/kg, ip), G-15 (5 μg/kg, ip), Saline, Ethanol and Dimethyl sulfoxide (DMSO) 30 min before each dose of PTZ. Observed seizures were classified between the phase 0–5. Thirty minutes later when the last 12. PTZ administration, all rats were sacrificed and the brain cortex, hippocampus sections were removed and the tissue superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) levels on these tissues were studied.ResultsGPER1 agonist, G-1 and estrogenic hormone, 17β-estradiol significantly increased the development of PTZ kindling the seizures. However, GPER1 antagonist, G-15 did not change the development of PTZ kindling the seizures. In the cortex and hippocampus homogenates, the NO levels after G-1 administration had significantly increased (p < 0.05) compared to the PTZ groups but SOD activities and MDA levels demonstrated no difference between the groups.ConclusionsThis is the first study that explores that GPER-1 receptors have epileptogenic effect on PTZ-induced kindling rat. GPER1 may mediate the epileptogenic effect of estrogens by changing the oxidative or anti-oxidative parameters in the brain.