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

Item Type:	Article
Title:	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
Creators Name:	Santolini, I. and Celli, R. and Cannella, M. and Imbriglio, T. and Guiducci, M. and Parisi, P. and Schubert, J. and Iacomino, M. and Zara, F. and Lerche, H. and Moyanova, S. and Ngomba, R.T. and van Luijtelaar, G. and Battaglia, G. and Bruno, V. and Striano, P. and Nicoletti, F.
Abstract:	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 THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). 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, 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.
Keywords:	Thrombospondins, Absence Epilepsy, α(2)δ Subunit, WAG/Rij rats, Genetic Variants, Animals, Rats
Source:	Epilepsia
ISSN:	0013-9580
Publisher:	Wiley
Volume:	58
Number:	11
Page Range:	1993-2001
Date:	November 2017
Additional Information:	Janine Altmüller is a member of the EuroEPINOMICS CoGIE Consortium.
Official Publication:	https://doi.org/10.1111/epi.13898
PubMed:	View item in PubMed

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