Can rodent models elucidate the pathomechanisms of genetic epilepsy?

Autosomal dominant sleep-related hypermotor epilepsy (ADSHE; previously autosomal dominant nocturnal frontal lobe epilepsy, ADNFLE), originally reported in 1994, was the first distinct genetic epilepsy shown to be caused by CHNRA4 mutation. In the past two decades, we have identified several functional abnormalities of mutant ion channels and their associated transmissions using several experiments involving single-cell and genetic animal (rodent) models. Currently, epileptologists understand that functional abnormalities underlying epileptogenesis/ictogenesis in humans and rodents are more complicated than previously believed and that the function of mutant molecules alone cannot contribute to the development of epileptogenesis/ictogenesis but play important roles in the development of epileptogenesis/ictogenesis through formation of abnormalities in various other transmission systems before epilepsy onset. Based on our recent findings using genetic rat ADSHE models, harbouring Chrna4 mutant, corresponding to human S284L-mutant CRHNA4, this review proposes a hypothesis associated with tripartite synaptic transmission in ADSHE pathomechanisms induced by mutant ACh receptors.

Automated summary

ADSHE, caused by CHNRA4 mutation, is a genetic epilepsy where mutant molecules play important roles in epileptogenesis/ictogenesis. Research involving experimental models has revealed the pathomechanisms of ADSHE, proposing a hypothesis associated with tripartite synaptic transmission induced by mutant ACh receptors.