Modulation of P2X Purinoceptor 3 (P2X3) in Pentylenetetrazole-Induced Kindling Epilepsy in Rats

Background: Epilepsy is a complex neurologic disorder with abnormal electrical impulses in the brain. A crucial role of purinergic signalling in the proper working of the nervous system has been reported but much less is known about the modulation of P2X3 purinergic receptors in epilepsy. This study investigated the effect of NF110, a potent P2X3 receptor antagonist, in the rat epilepsy model of pentylenetetrazole (PTZ)-induced kindling. Material/Methods: The mean kindling score, motor activity, locomotion, emotional tension, anxiety, discrimination ability, learning, memory, serum neuron-specific enolase (sNSE), hippocampal IL-1 beta and TNF-alpha, thiobarbituric acid-reactive substance (TBARS), catalase (CAT) and reduced glutathione (GSH), and mitochondria) complex I, II, and IV levels of PTZ-kindling animals were assessed. Results: The PTZ-kindling animals have shown impaired motor activity, locomotion, discrimination ability, learning, and memory, along with increased emotional tension, anxiety, neuronal damage (increased sNSE), hippocampal proinflammatory mediators (increased IL-1 beta and TNF-alpha), oxidative stress (increased TBARS, decreased GSH and CAT), and mitochondria) dysfunction. The administration of NF110 in 3 different doses has significantly and dose-dependently corrected PTZ-kindling-induced impaired behavior, learning, memory, locomotion, motor activity, discrimination ability, neuronal damage, hippocampal inflammation, oxidative stress, and mitochondrial dysfunction. These beneficial effects of NF110 in PTZ-kindling animals were significantly abolished by the administration of the P2X agonist alpha, beta methylene-ATP. Conclusions: P2X3 receptors play a very important role in kindling epilepsy and further research should be done to design P2X3 modulators for their possible therapeutic benefits in epileptic disorders.