title: Ca2+-permeable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma.
abstract: Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca2+permeability through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues. In HH, however, these activities were clearly abolished by application of Joro Spider Toxin (JSTX), a specific inhibitor of the Ca2+-permeable AMPA receptor. Consistent with these physiologic findings, the neuronal nuclei showed disappearance of adenosine deaminase acting on RNA 2 (ADAR2) immunoreactivity. Furthermore, examination of glutamate receptor 2 (GluA2) messenger RNA (mRNA) revealed that editing efficiency at the glutamine/arginine site was significantly low. These results suggest that neurons in HH may bear Ca2+-permeable AMPA receptors due to dislocation of ADAR2.
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kitaura
authors.affiliation: Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sonoda
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Teramoto
authors.affiliation: Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shirozu
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masuda
authors.affiliation: Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kwak
authors.affiliation: Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kameyama
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000378:metabolism*; D002648:Child; D004569:Electroencephalography; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000209:etiology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006222:Hamartoma / Q000150:complications* / Q000000981:diagnostic imaging; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications* / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium
keywords: ADAR2; Human tissue; Hypothalamic hamartoma; Joro Spider Toxin; RNA editing