Alterations in the α2δ ligand, thrombospondin‐1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies

• Published in: Epilepsia (Copenhagen) Vol. 58; no. 11; pp. 1993 - 2001
• Main 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, Luijtelaar, Gilles, Battaglia, Giuseppe, Bruno, Valeria, Striano, Pasquale, Nicoletti, Ferdinando, Palotie, Aarno, Folkhälsan, Anna‐Elina Lehesjoki, Ruppert, Ann‐Kathrin, Siren, Auli, Koeleman, Bobby, Lal, Dennis, Becker, Felicitas, Caglayan, Hande, Hjalgrim, Helle, Muhle, Hiltrud, Thiele, Holger, Helbig, Ingo, Altmuller, Janine, Jabbari, Kamel, Everett, Kate, May, Patrick, Nurnberg, Peter, Møller, Rikke, Nabbout, Rima, Krause, Roland, Balling, Rudi, Baulac, Stephanie, Sander, Thomas, Kunz, Wolfram, Weber, Yvonne, Bianchi, Amedeo, La Neve, Angela, Coppola, Antonietta, Striano, Salvatore, Capovilla, Giuseppe, Ferlazzo, Edoardo, Bagnasco, Irene, Ferretti, Alessandro, Di Bonaventura, Carlo, Vari, Maria Stella, Pinto, Francesca, Bisulli, Francesca, Tinuper, Paolo, Minetti, Carlo, Belcastro, Vincenzo, Giordano, Lucio, Gambardella, Antonio
• Format: Journal Article
• Language: English
• Published: 01.11.2017
• Subjects: Absence epilepsy; Genetic variants; Thrombospondins; WAG/Rij rats; α2δ subunit
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.13898

Summary Objectives Thrombospondins, which are known to interact with the α2δ 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 α2δ subunit, and protein levels of α2δ, 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.