title: Phosphorylation of NMDA 2B at S1303 in human glioma peritumoral tissue: implications for glioma epileptogenesis.
abstract: OBJECTIVE
  Peritumoral seizures are an early symptom of a glioma. To gain a better understanding of the molecular mechanism underlying tumor-induced epileptogenesis, the authors studied modulation of the N-methyl-d-aspartate (NMDA) receptor in peritumoral tissue.
  
  
  METHODS
  To study the possible etiology of peritumoral seizures, NMDA receptor expression, posttranslational modification, and function were analyzed in an orthotopic mouse model of human gliomas and primary patient glioma tissue in which the peritumoral border (tumor-brain interface) was preserved in a tissue block during surgery.
  
  
  RESULTS
  The authors found that the NMDA receptor containing the 2B subunit (NR2B), a predominantly extrasynaptic receptor, is highly phosphorylated at S1013 in the neurons located in the periglioma area of the mouse brain. NR2B is also highly phosphorylated at S1013 in the neurons located in the peritumoral area from human brain tissue containing a glioma. The phosphorylation of the extrasynaptic NMDA receptor increases its permeability for Ca(2+) influx and subsequently mediates neuronal overexcitation and seizure activity.
  
  
  CONCLUSIONS
  These data suggest that overexcitation of the extrasynaptic NMDA receptors in the peritumoral neurons may contribute to the development of peritumoral seizures and that the phosphorylated NR2B may be a therapeutic target for blocking primary brain tumor-induced peritumoral seizures.
authors.affiliation: Goodman Campbell Brain and Spine, Department of Neurological Surgery, Indiana University School of Medicine;
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Shanbao
authors.initials: S
authors.lastname: Cai
authors.forename: M Reza
authors.initials: MR
authors.lastname: Saadatzadeh
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Karen E
authors.initials: KE
authors.lastname: Pollok
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Cohen-Gadol
authors.forename: Jinhui
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D051747:DNA-Activated Protein Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation / Q000379:methods; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C121001:NR2B NMDA receptor; D009687:Nuclear Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D012694:Serine; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse
keywords: DAPI = 4′,6-diamidino-2-phenylindole; EGFP = enhanced green fluorescent protein; FBS = fetal bovine serum; GBM = glioblastoma multiforme; GFAP = glial fibrillary acidic protein; Glu = glutamate; NMDA; NMDA = N-methyl-d-aspartate; NMDAR = NMDA receptor; NR2B; NR2B = NMDA receptor containing 2B subunit; NeuN = neuron-specific nuclear protein; PBS = phosphate-buffered saline; glioblastoma multiforme; pNR2B = phosphorylated NR2B; peritumoral seizures