title: Altered expression of neurotransmitter-receptor subunit and uptake site mRNAs in hemimegalencephaly.
abstract: OBJECTIVE
  Hemimegalencephaly (HMEG) is characterized by unilateral hemispheric enlargement and severe cytoarchitectural abnormalities that are highly associated with intractable epilepsy. No studies have defined alterations in neurotransmitter-receptor subunit gene expression in HMEG. We hypothesize that a differential expression of excitatory amino acid and gamma-aminobutyric acid (GABA)A-receptor subunit messenger RNAs (mRNAs) exists in HMEG.
  
  
  METHODS
  The expression of mRNAs encoding 20 neurotransmitter-receptor subunits, synthetic enzymes, and uptake sites as well as select additional candidate genes was defined in HMEG samples (n=8) compared with homotopic control cortex specimens by using targeted complementary DNA (cDNA) arrays. Expression of GLT-1 (a glial glutamate transporter), EAAC-1 (neuronal glutamate transporter), and NMDA2B was corroborated by immunohistochemical, Western, and ligand-binding assays.
  
  
  RESULTS
  Differential expression of 11 neurotransmitter-related mRNAs was demonstrated in HMEG compared with control cortex. For example, expression of GLT-1 and GluR6 mRNAs was enhanced, whereas diminished expression of the neuronal glutamate transporter EAAC-1, GABAAalpha2, GABAAgamma2, GABAAgamma3, NMDA2B, GluR1, GluR2, GluR4, and GluR5 subunits occurred. Reduced NMDA2B subunit mRNA expression in HMEG was confirmed by receptor ligand-binding assays by using the NMDA2B-receptor antagonist ifenprodil, which revealed barely detectable levels of NMDA2B binding compared with that in control cortex.
  
  
  CONCLUSIONS
  Selective alterations occur in distinct neurotransmitter-receptor and -uptake sites in HMEG. Differential expression of neurotransmitter-receptor and -uptake sites in HMEG may contribute to epileptogenesis in HMEG.
authors.affiliation: PENN Epilepsy Center, Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Marianna
authors.initials: M
authors.lastname: Baybis
authors.forename: David
authors.initials: D
authors.lastname: Lynch
authors.forename: Allana
authors.initials: A
authors.lastname: Lee
authors.forename: Anita
authors.initials: A
authors.lastname: Patel
authors.forename: Guy
authors.initials: G
authors.lastname: McKhann
authors.forename: Diane
authors.initials: D
authors.lastname: Chugani
authors.forename: William
authors.initials: W
authors.lastname: J Kupsky
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Peter B
authors.initials: PB
authors.lastname: Crino
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002540:Cerebral Cortex / Q000002:abnormalities / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D042787:Receptor, TIE-2; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*
chemical_list: D027342:Excitatory Amino Acid Transporter 2; C121001:NR2B NMDA receptor; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D042787:Receptor, TIE-2