{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:15:21Z","timestamp":1740125721440,"version":"3.37.3"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T00:00:00Z","timestamp":1505433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Thrombospondins, which are known to interact with the \u03b1<jats:sub>2<\/jats:sub>\u03b4 subunit of voltage\u2010sensitive 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\u20101 was altered in the brain of <jats:styled-content style=\"fixed-case\">WAG<\/jats:styled-content>\/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of <jats:italic><jats:styled-content style=\"fixed-case\">THBS<\/jats:styled-content>1<\/jats:italic> in a large cohort of children affected by idiopathic\/genetic generalized epilepsies (<jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">GGE<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured the transcripts of thrombospondin\u20101 and \u03b1<jats:sub>2<\/jats:sub>\u03b4 subunit, and protein levels of \u03b1<jats:sub>2<\/jats:sub>\u03b4, Rab3A, and the vesicular glutamate transporter, <jats:styled-content style=\"fixed-case\">VGLUT<\/jats:styled-content>1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic <jats:styled-content style=\"fixed-case\">WAG<\/jats:styled-content>\/Rij rats and in two control strains by real\u2010time polymerase chain reaction (<jats:styled-content style=\"fixed-case\">PCR)<\/jats:styled-content> and immunoblotting. We examined the genetic variants of <jats:italic><jats:styled-content style=\"fixed-case\">THBS<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">CACNA<\/jats:styled-content>2D1<\/jats:italic> in two independent cohorts of patients affected by <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">GGE<\/jats:styled-content> recruited through the Genetic Commission of the Italian League Against Epilepsy (<jats:styled-content style=\"fixed-case\">LICE<\/jats:styled-content>) and the Euro<jats:styled-content style=\"fixed-case\">EPINOMICS<\/jats:styled-content>\u2010Co<jats:styled-content style=\"fixed-case\">GIE<\/jats:styled-content> Consortium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thrombospondin\u20101 <jats:styled-content style=\"fixed-case\">messenger RNA (mRNA<\/jats:styled-content>) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic <jats:styled-content style=\"fixed-case\">WAG<\/jats:styled-content>\/Rij rats, whereas levels in the somatosensory cortex were unchanged. <jats:styled-content style=\"fixed-case\">VGLUT<\/jats:styled-content>1 protein levels were also reduced in the ventrobasal thalamus of <jats:styled-content style=\"fixed-case\">WAG<\/jats:styled-content>\/Rij rats. Genetic variants of <jats:italic><jats:styled-content style=\"fixed-case\">THBS<\/jats:styled-content>1<\/jats:italic> were significantly more frequent in patients affected by <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">GGE<\/jats:styled-content> than in nonepileptic controls, whereas the frequency of <jats:italic><jats:styled-content style=\"fixed-case\">CACNA<\/jats:styled-content>2D1<\/jats:italic> was unchanged.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These findings suggest that thrombospondin\u20101 may have a role in the pathogenesis of <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">GGE<\/jats:styled-content>s.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13898","type":"journal-article","created":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T05:56:42Z","timestamp":1505455002000},"page":"1993-2001","source":"Crossref","is-referenced-by-count":7,"title":["Alterations in the \u03b1<sub>2<\/sub>\u03b4 ligand, thrombospondin\u20101, in a rat model of spontaneous absence epilepsy and in patients with idiopathic\/genetic generalized epilepsies"],"prefix":"10.1111","volume":"58","author":[{"given":"Ines","family":"Santolini","sequence":"first","affiliation":[{"name":"I.R.C.C.S. 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