Alterations in the α2δ ligand, thrombospondin‐1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies. (15th September 2017)

• Record Type: Journal Article
• Authors: Santolini, Ines; Celli, Roberta; Cannella, Milena; Imbriglio, Tiziana; Guiducci, Michela; Parisi, Pasquale; Schubert, Julian; Iacomino, Michele; Zara, Federico; Lerche, Holger; Moyanova, Slavianka; Ngomba, Richard Teke; van Luijtelaar, Gilles; Battaglia, Giuseppe; Bruno, Valeria; Striano, Pasquale; Nicoletti, Ferdinando
• Other Names: Palotie Aarno investigator.; Folkhälsan Anna‐Elina Lehesjoki investigator.; Ruppert Ann‐Kathrin investigator.; Siren Auli investigator.; Koeleman Bobby investigator.; Lal Dennis investigator.; Becker Felicitas investigator.; Caglayan Hande investigator.; Hjalgrim Helle investigator.; Muhle Hiltrud investigator.; Thiele Holger investigator.; Helbig Ingo investigator.; Altmuller Janine investigator.; Jabbari Kamel investigator.; Everett Kate investigator.; May Patrick investigator.; Nurnberg Peter investigator.; Møller Rikke investigator.; Nabbout Rima investigator.; Krause Roland investigator.; Balling Rudi investigator.; Baulac Stephanie investigator.; Sander Thomas investigator.; Kunz Wolfram investigator.; Weber Yvonne investigator.; Bianchi Amedeo investigator.; La Neve Angela investigator.; Coppola Antonietta investigator.; Striano Salvatore investigator.; Capovilla Giuseppe investigator.; Ferlazzo Edoardo investigator.; Bagnasco Irene investigator.; Ferretti Alessandro investigator.; Di Bonaventura Carlo investigator.; Vari Maria Stella investigator.; Pinto Francesca investigator.; Bisulli Francesca investigator.; Tinuper Paolo investigator.; Minetti Carlo investigator.; Belcastro Vincenzo investigator.; Giordano Lucio investigator.; Gambardella Antonio investigator.;
• Is Part Of: Epilepsia. Volume 58:issue 11(2017)
• Page Start: 1993
• Page End: 2001
• Publication Date: 2017-09-15
• Subjects: Thrombospondins -- Absence epilepsy -- α2δ subunit -- WAG/Rij rats -- Genetic variants; Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.13898
• Languages: English
• ISSNs: 0013-9580

Abstract

Summary: Objectives: Thrombospondins, which are known to interact with the α2 δ subunit of voltage‐sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin‐1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). Methods: We measured the transcripts of thrombospondin‐1 and α2 δ subunit, and protein levels of α2 δ, Rab3A, and the vesicular glutamate transporter, VGLUT1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic WAG/Rij rats and in two control strains by real‐time polymerase chain reaction (PCR) and immunoblotting. We examined the genetic variants of THBS1 and CACNA2D1 in two independent cohorts of patients affected by IGE/GGE recruited through the Genetic Commission of the Italian League Against Epilepsy (LICE) and the EuroEPINOMICS‐CoGIE Consortium. Results: Thrombospondin‐1 messenger RNA (mRNA) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic WAG/Rij rats, whereas levels in the somatosensory cortex were unchanged. VGLUT1 protein levels were also reduced in the ventrobasal thalamus of WAG/Rij rats. Genetic variants of THBS1 were significantly more frequent in patients affected by IGE/GGE than in nonepileptic controls, whereas the frequency of CACNA2D1 was unchanged. Significance: These findings suggest that thrombospondin‐1 may have a role in the pathogenesis of IGE/GGEs.