The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels?

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

Journal Name: Current Neuropharmacology

Volume 15 , Issue 6 , 2017

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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.

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

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Article Details

VOLUME: 15
ISSUE: 6
Year: 2017
Page: [918 - 925]
Pages: 8
DOI: 10.2174/1570159X15666170309105451
Price: $58

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