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The α(2)δ Subunit and Absence Epilepsy: Beyond Calcium Channels?
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) contrib...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Science Publishers
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652034/ https://www.ncbi.nlm.nih.gov/pubmed/28290248 http://dx.doi.org/10.2174/1570159X15666170309105451 |
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author | Celli, Roberta Santolini, Ines Guiducci, Michela van Luijtelaar, Gilles Parisi, Pasquale Striano, Pasquale Gradini, Roberto Battaglia, Giuseppe Ngomba, Richard T. Nicoletti, Ferdinando |
author_facet | Celli, Roberta Santolini, Ines Guiducci, Michela van Luijtelaar, Gilles Parisi, Pasquale Striano, Pasquale Gradini, Roberto Battaglia, Giuseppe Ngomba, Richard T. Nicoletti, Ferdinando |
author_sort | Celli, Roberta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5652034 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-56520342018-02-01 The α(2)δ 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 Curr Neuropharmacol Article 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. Bentham Science Publishers 2017-08 2017-08 /pmc/articles/PMC5652034/ /pubmed/28290248 http://dx.doi.org/10.2174/1570159X15666170309105451 Text en © 2017 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/legalcode This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Article Celli, Roberta Santolini, Ines Guiducci, Michela van Luijtelaar, Gilles Parisi, Pasquale Striano, Pasquale Gradini, Roberto Battaglia, Giuseppe Ngomba, Richard T. Nicoletti, Ferdinando The α(2)δ Subunit and Absence Epilepsy: Beyond Calcium Channels? |
title | The α(2)δ Subunit and Absence Epilepsy: Beyond Calcium Channels? |
title_full | The α(2)δ Subunit and Absence Epilepsy: Beyond Calcium Channels? |
title_fullStr | The α(2)δ Subunit and Absence Epilepsy: Beyond Calcium Channels? |
title_full_unstemmed | The α(2)δ Subunit and Absence Epilepsy: Beyond Calcium Channels? |
title_short | The α(2)δ Subunit and Absence Epilepsy: Beyond Calcium Channels? |
title_sort | α(2)δ subunit and absence epilepsy: beyond calcium channels? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652034/ https://www.ncbi.nlm.nih.gov/pubmed/28290248 http://dx.doi.org/10.2174/1570159X15666170309105451 |
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