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Alterations in the α 2 δ ligand, thrombospondin‐1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies
Author(s) -
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
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13898
Subject(s) - epileptogenesis , idiopathic generalized epilepsy , epilepsy , thalamus , biology , neuroscience , childhood absence epilepsy , genetic model , medicine , genetics , endocrinology , gene
Summary Objectives Thrombospondins, which are known to interact with the α 2 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 THBS 1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies ( IGE / GGE s). Methods We measured the transcripts of thrombospondin‐1 and α 2 δ subunit, and protein levels of α 2 δ, Rab3A, and the vesicular glutamate transporter, VGLUT 1, 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 THBS 1 and CACNA 2D1 in two independent cohorts of patients affected by IGE / GGE recruited through the Genetic Commission of the Italian League Against Epilepsy ( LICE ) and the Euro EPINOMICS ‐Co GIE 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. VGLUT 1 protein levels were also reduced in the ventrobasal thalamus of WAG /Rij rats. Genetic variants of THBS 1 were significantly more frequent in patients affected by IGE / GGE than in nonepileptic controls, whereas the frequency of CACNA 2D1 was unchanged. Significance These findings suggest that thrombospondin‐1 may have a role in the pathogenesis of IGE / GGE s.