The α2δ subunit and absence epilepsy: Beyond calcium channels?

Roberta Celli, Ines Santolini, Michela Guiducci, Gilles Van Luijtelaar, Pasquale Parisi, Pasquale Striano, Roberto Gradini, Giuseppe Battaglia, Richard T. Ngomba, Ferdinando Nicoletti

Research output: Contribution to journalReview articlepeer-review

Abstract

Background: Spike-wave discharges, underlying absence seizures, are generated within a cortico-thalamo-cortical network that involves the somatosensory cortex, the reticular thalamic nucleus, and the ventrobasal thalamic nuclei. Activation of T-type voltage-sensitive calcium channels (VSCCs) contributes to the pathological oscillatory activity of this network, and some of the first-line drugs used in the treatment of absence epilepsy inhibit T-type calcium channels. The α2δ subunit is a component of high voltage-activated VSCCs (i.e., L-, N-, P/Q-, and R channels) and studies carried out in heterologous expression systems suggest that it may also associate with T channels. The α2δ subunit is also targeted by thrombospondins, which regulate synaptogenesis in the central nervous system. Objective: To discuss the potential role for the thrombospondin/α2δ axis in the pathophysiology of absence epilepsy. Methods: We searched PubMed articles for the terms “absence epilepsy”, “T-type voltage-sensitive calcium channels”, “α2δ subunit”, “ducky mice”, “pregabalin”, “gabapentin”, “thrombospondins”, and included papers focusing this Review's scope. Results: We moved from the evidence that mice lacking the α2δ-2 subunit show absence seizures and α2δ ligands (gabapentin and pregabalin) are detrimental in the treatment of absence epilepsy. This suggests that α2δ may be protective against absence epilepsy via a mechanism that does not involve T channels. We discuss the interaction between thrombospondins and α2δ and its potential relevance in the regulation of excitatory synaptic formation in the cortico-thalamo-cortical network. Conclusion: We speculate on the possibility that the thrombospondin/α2δ axis is critical for the correct functioning of the cortico-thalamo-cortical network, and that abnormalities in this axis may play a role in the pathophysiology of absence epilepsy.

Original languageEnglish
Pages (from-to)918-925
Number of pages8
JournalCurrent Neuropharmacology
Volume15
Issue number6
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Absence epilepsy
  • Ducky mice
  • Gabapentin
  • Non-T-type voltage-sensitive Ca channels
  • Pregabalin
  • T-type voltage-sensitive Ca channels
  • Thrombospondins
  • αδ subunit

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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