| Title: |
The α2δ subunit and absence epilepsy: Beyond calcium channels? |
| Authors: |
Celli R.; Santolini I.; Guiducci M.; Van Luijtelaar G.; Parisi P.; Striano P.; Gradini R.; Battaglia G.; Ngomba R. T.; Nicoletti F. |
| Contributors: |
Celli, R.; Santolini, I.; Guiducci, M.; Van Luijtelaar, G.; Parisi, P.; Striano, P.; Gradini, R.; Battaglia, G.; Ngomba, R. T.; Nicoletti, F. |
| Publisher Information: |
Bentham Science Publishers B.V.; ;P.O. Box 294 |
| Publication Year: |
2017 |
| Collection: |
Università degli Studi di Genova: CINECA IRIS |
| Subject Terms: |
Absence epilepsy; Ducky mice; Gabapentin; Non-T-type voltage-sensitive Ca; 2+; channel; Pregabalin; T-type voltage-sensitive Ca; Thrombospondin; α; δ subunit |
| Time: |
2 |
| 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/WOS:000407196400009; volume:15; firstpage:918; lastpage:925; numberofpages:8; journal:CURRENT NEUROPHARMACOLOGY; https://hdl.handle.net/11567/1022081 |
| DOI: |
10.2174/1570159X15666170309105451 |
| Availability: |
https://hdl.handle.net/11567/1022081; https://doi.org/10.2174/1570159X15666170309105451 |
| Rights: |
info:eu-repo/semantics/closedAccess |
| Accession Number: |
edsbas.9B7F59F4 |
| Database: |
BASE |