The Orexin System: A Potential Player in the Pathophysiology of Absence Epilepsy

Background: Absence epilepsy is characterized by the presence of spike-and-wave discharges (SWDs) at the EEG generated within the cortico-thalamo-cortical circuit. The molecular mechanisms involved in the pathophysiology of absence epilepsy are only partially known. WAG/Rij rats older than 2-3 months develop spontaneous SWDs, and they are sensitive to anti-absence medications. Hence, WAG/Rij rats are extensively used as a model for absence epilepsy with predictive validity. Objective: The aim of the study was to examine the possibility that the orexin system, which supports the wake status in experimental animals and humans, plays a role in the pathophysiology of absence seizures. Methods: The perspective grounds its method from recent literature along with measurements of orexin receptor type-1 (OX1) protein levels in the thalamus and somatosensory cortex of WAG/Rij rats and non-epileptic Wistar control rats at two ages (25 days and 6-7 months). OX1 protein levels were measured by immunoblotting. Results: The analysis of the current literature suggests that the orexin system might be involved in the pathophysiology of absence epilepsy and might be targeted by therapeutic intervention. Experimental data are in line with this hypothesis, showing that OX1 protein levels were reduced in the thalamus and somatosensory cortex of symptomatic WAG/Rij rats (6-7 months of age) with respect to non-epileptic controls, whereas these differences were not seen in pre-symptomatic, 25 days-old WAG/Rij rats. Conclusion: This perspective might pave the way for future studies on the involvement of the orexinergic system in the pathophysiology of SWDs associated with absence epilepsy and its comorbidities.