title: Expression of astrocyte-related receptors in cortical dysplasia with intractable epilepsy.
abstract: Epilepsy is one of the major neurologic diseases, and astrocytes play important roles in epileptogenesis. To investigate possible roles of astrocyte-related receptors in patients with intractable epilepsy associated with focal cortical dysplasia (FCD) and other conditions, we examined resected epileptic foci from 31 patients, including 23 with FCD type I, IIa, or IIb, 5 with tuberous sclerosis complex, and 3 with low-grade astrocytoma. Control samples were from 21 autopsied brains of patients without epilepsy or neurologic deficits and 5 patients with pathologic gliosis without epilepsy. Immunohistochemical and immunoblot analyses with antibodies against purinergic receptor subtypes P2RY1, P2RY2, P2RY4, potassium channels Kv4.2 and Kir4.1, and metabotropic receptor subtypes mGluR1 and mGluR5 were performed. Anti-glial fibrillary acidic protein, anti-NeuN, and anti-CD68 immunostaining was used to identify astrocytes, neurons, and microglia, respectively. Most glial fibrillary acidic protein-immunopositive astrocyte cells in the brain samples from patients with epilepsy were P2RY1-, P2RY2-, P2RY4-, Kv4.2-, Kir4.1-, mGluR1-, and mGluR5-positive, whereas samples from controls and pathologic gliosis showed lower expression levels of these astrocyte-related receptors. Our findings suggest that, although these receptors are necessary for astrocyte transmission, formation of the neuron-glia network, and other physiologic functions, overexpression in the brains of patients with intractable epilepsy may be associated with activation of intracellular and glio-neuronal signaling pathways that contribute to epileptogenesis.
authors.affiliation: From the Epilepsy Center (SS, TO, SH, RH, TS, EN, TK, NS, YK, AT, KS, YS, MS, YG, MI), Departments of Mental Retardation and Birth Defect Research (SS, HD, SN, SH, YG, MI), Neurosurgery (TO, TK, YK, AT), Child Neurology (RH, TS, EN, KS, MS), Radiology (NS), and Laboratory Medicine (YS), National Center of Neurology and Psychiatry, Kodaira, Tokyo; and Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi (SS, SH, SK), Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Sukigara
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dai
authors.forename: Shin
authors.initials: S
authors.lastname: Nabatame
authors.forename: Taisuke
authors.initials: T
authors.lastname: Otsuki
authors.forename: Sae
authors.initials: S
authors.lastname: Hanai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Honda
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakagawa
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kaido
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.forename: Yuu
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Akio
authors.initials: A
authors.lastname: Takahashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Schuichi
authors.initials: S
authors.lastname: Koizumi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D004172:Diplopia / Q000150:complications* / Q000473:pathology*; D004827:Epilepsy / Q000150:complications* / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D058469:Receptors, Purinergic P2X / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000098854:Kcnj10 Channel
chemical_list: D005904:Glial Fibrillary Acidic Protein; D000098854:Kcnj10 Channel; C489469:Kir4.2 channel; D024661:Potassium Channels, Inwardly Rectifying; D018094:Receptors, Metabotropic Glutamate; D058469:Receptors, Purinergic P2X; C073111:metabotropic quisqualate receptor