The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels?

Title:The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels?

Volume: 15 Issue: 6

Author(s): Roberta Celli, Ines Santolini, Michela Guiducci, Gilles van Luijtelaar, Pasquale Parisi, Pasquale Striano, Roberto Gradini, Giuseppe Battaglia, Richard T. Ngomba and Ferdinando Nicoletti*

Affiliation:

• Department of Physiology and Pharmacology, University Sapienza, Piazzale Aldo Moro, 5, 00185 Rome,Italy

Keywords: α2δ subunit, T-type voltage-sensitive Ca²⁺ channels, non-T-type voltage-sensitive Ca²⁺ channels, ducky mice, pregabalin, gabapentin, absence epilepsy, thrombospondins.

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 α 2δ 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/α2 δ 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.

Cite this article as:

Celli Roberta , Santolini Ines , Guiducci Michela , van Luijtelaar Gilles , Parisi Pasquale, Striano Pasquale , Gradini Roberto , Battaglia Giuseppe , Ngomba T. Richard and Nicoletti Ferdinando*, The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels?, Current Neuropharmacology 2017; 15 (6) . https://dx.doi.org/10.2174/1570159X15666170309105451

DOI https://dx.doi.org/10.2174/1570159X15666170309105451	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190