title: Upregulation of RBFOX1 in the malformed cortex of patients with intractable epilepsy and in cultured rat neurons.
abstract: Mutations in RNA‑binding Fox 1 (RBFOX1) are known to be associated with neurodevelopmental disorders including epilepsy, mental retardation and autism spectrum disorder. The deletion of the Rbfox1 gene in mice has been shown to result in heightened susceptibility to seizures. However, other studies have revealed mutations or the downregulation of RBFOX1 in specimens obtained from patients with epilepsy or malformations of cortical development (MCD). Generally, the expression of RBFOX1 varies according to tissue type. In this study, we demonstrated the upregulation of RBFOX1 protein in the cortex of patients with MCD and intractable epilepsy. Electrophysiological recordings of cultured rat cortical neurons with increased Rbfox1 expression also revealed a significantly increased amplitude of action potential (AP) and Na+ current density. Some of these neurons (26.32%) even displayed spontaneous, recurrent, epileptiform discharges (SREDs). Additionally, certain Rbfox1 target transcripts associated with epilepsy, including glutamate receptor, ionotropic, N-methyl D-aspartate 1 [Grin1, also known as N-methyl-D-aspartate receptor subunit NR1 (NMDAR1)], synaptosomal-associated protein, 25 kDa (SNAP‑25 or Snap25) and sodium channel, voltage gated, type VIII, alpha subunit (Scn8a, also known as Nav1.6) were identified to be upregulated in these cultured cortical neurons with an upregulated Rbfox1 expression. These data suggest that the upregulation of RBFOX1 contributes to neuronal hyperexcitation and seizures. The upregulation of NMDAR1 (Grin1), SNAP‑25 (Snap25) and Scn8a may thus be involved in Rbfox1‑related neuronal hyperexcitation.
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wen
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Neurology, University‑Town Hospital of Chongqing Medical University, Chongqing 401331, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yan
authors.affiliation: Department of Neurology, Xi'an Central Hospital, Xi'an 710003, P.R. China.
authors.forename: Xiao Shan
authors.initials: XS
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Shi Yong
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Neurology, Afﬁliated Hospital of Guiyang Medical University, Guiyang 550004, P.R. China.
authors.forename: Zhan Hui
authors.initials: ZH
authors.lastname: Feng
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000378:metabolism*; D002648:Child; D004827:Epilepsy / Q000209:etiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins