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Altered Expression of Neurotransmitter‐receptor Subunit and Uptake Site mRNAs in Hemimegalencephaly
Author(s) -
Baybis Marianna,
Lynch David,
Lee Allana,
Patel Anita,
McKhann Guy,
Chugani Diane,
J.Kupsky William,
Aronica Eleonora,
Crino Peter B.
Publication year - 2004
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.0013-9580.2004.16204.x
Subject(s) - ifenprodil , neurotransmitter receptor , glutamate receptor , neurotransmitter , biology , epileptogenesis , microbiology and biotechnology , receptor , gene expression , biochemistry , neuroscience , gene , hippocampus
Summary: Purpose: 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 γ‐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, GABA A α2, GABA A γ2, GABA A γ3, 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.