The role of the nicotinic acetylcholine receptors in sleep-related epilepsy

Carla Marini, Renzo Guerrini

Research output: Contribution to journalArticlepeer-review

Abstract

The role of neuronal acetylcholine receptors (nAChRs) in epilepsy has been clearly established by the finding of mutations in a subset of genes coding for subunits of the nAChRs in a form of sleep-related epilepsy with familial occurrence in about 30% of probands and dominant inheritance, named autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sporadic and familial forms have similar clinical and EEG features. Seizures begin in middle childhood as clusters of sleep-related attacks with prominent motor activity, and sustained dystonic posturing. In addition to nocturnal seizures, psychosis or schizophrenia, behavioral disorders, memory deficits and mental retardation were described in some individuals. Although over hundred families are on record, only a minority of them have been linked to mutations in the genes coding for the α4, α2 and β2 (CHRNA4, CHRNA2, and CHRNB2) subunits of the nAChRs, indicating that ADNFLE is genetically heterogeneous despite a relatively homogeneous clinical picture. Functional characterization of some mutations suggests that gain of the receptor function might be the basis for epileptogenesis. In vitro and in vivo studies have shown high density of nAChRs in the thalamus, over activated brainstem ascending cholinergic pathway and enhanced GABAergic function, reinforcing the hypothesis that cortico-subcortical networks, regulating arousal from sleep, play a central role in seizure precipitation in ADNFLE.

Original languageEnglish
Pages (from-to)1308-1314
Number of pages7
JournalBiochemical Pharmacology
Volume74
Issue number8
DOIs
Publication statusPublished - Oct 15 2007

Keywords

  • Acetylcholine receptors
  • ADNFLE
  • CHRNA2
  • CHRNA4
  • CHRNB2
  • Idiopathic focal epilepsy

ASJC Scopus subject areas

  • Pharmacology

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