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 journalArticle

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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.

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

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Absence Epilepsy
Calcium Channels
Thrombospondins
Thalamic Nuclei
T-Type Calcium Channels
Somatosensory Cortex
PubMed
Central Nervous System
Ligands

Keywords

  • Journal Article

Cite this

Celli, R., Santolini, I., Guiducci, M., van Luijtelaar, G., Parisi, P., Striano, P., ... Nicoletti, F. (2017). The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels? Current Neuropharmacology, 15(6), 918-925. https://doi.org/10.2174/1570159X15666170309105451

The α2δ Subunit and Absence Epilepsy : Beyond Calcium Channels? / Celli, Roberta; Santolini, Ines; Guiducci, Michela; van Luijtelaar, Gilles; Parisi, Pasquale; Striano, Pasquale; Gradini, Roberto; Battaglia, Giuseppe; Ngomba, Richard T; Nicoletti, Ferdinando.

In: Current Neuropharmacology, Vol. 15, No. 6, 2017, p. 918-925.

Research output: Contribution to journalArticle

Celli, R, Santolini, I, Guiducci, M, van Luijtelaar, G, Parisi, P, Striano, P, Gradini, R, Battaglia, G, Ngomba, RT & Nicoletti, F 2017, 'The α2δ Subunit and Absence Epilepsy: Beyond Calcium Channels?', Current Neuropharmacology, vol. 15, no. 6, pp. 918-925. https://doi.org/10.2174/1570159X15666170309105451
Celli, Roberta ; Santolini, Ines ; Guiducci, Michela ; van Luijtelaar, Gilles ; Parisi, Pasquale ; Striano, Pasquale ; Gradini, Roberto ; Battaglia, Giuseppe ; Ngomba, Richard T ; Nicoletti, Ferdinando. / The α2δ Subunit and Absence Epilepsy : Beyond Calcium Channels?. In: Current Neuropharmacology. 2017 ; Vol. 15, No. 6. pp. 918-925.
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AU - Celli, Roberta

AU - Santolini, Ines

AU - Guiducci, Michela

AU - van Luijtelaar, Gilles

AU - Parisi, Pasquale

AU - Striano, Pasquale

AU - Gradini, Roberto

AU - Battaglia, Giuseppe

AU - Ngomba, Richard T

AU - Nicoletti, Ferdinando

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PY - 2017

Y1 - 2017

N2 - 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.

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