Impaired maturation of cortical GABAA receptor expression in pediatric epilepsy

Laura A. Jansen, Lindsey D. Peugh, William H. Roden, Jeffrey G. Ojemann

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Purpose: Expression of the protein subunits that make up the -aminobutyric acid (GABA)A receptor pentamer is known to change during postnatal brain development in animal models. In the present study, analysis of cortical GABAA subunit expression was performed in control human tissue obtained from infancy through adolescence, and was compared to that from similarly aged children with intractable focal epilepsy. Methods: Twenty frozen pediatric control and 25 epileptic neocortical specimens were collected. The membrane fractions were isolated and subjected to quantitative western blot analysis. Subunit expression was correlated with clinical factors including age, pathology, and medication exposure. Results: In control cortical samples, 1 and 2 GABAA receptor subunits exhibited low expression in infancy, which increased over the first several years of life and then stabilized through adolescence. In contrast, 4 subunit expression was higher in infants than in older children. The level of the chloride transporter KCC2 increased markedly with age, whereas that of NKCC1 decreased. These patterns were absent in the children with epilepsy, both in those with focal cortical dysplasia and in those with cortical gliosis. Although there was marked variability in GABAA receptor subunit expression among the children with epilepsy, identifiable patterns of subunit expression were found in each individual child. Discussion: Maturation of cortical GABAA receptor subunit expression continues over the first several years of postnatal human development. Intractable focal epilepsy in children is associated with disruption of this normal developmental pattern. These findings have significant implications for the treatment of children with medications that modulate GABAA receptor function.

Original languageEnglish
Pages (from-to)1456-1467
Number of pages12
JournalEpilepsia
Volume51
Issue number8
DOIs
StatePublished - Aug 2010

Keywords

  • Cerebral cortex
  • Development
  • Epilepsy
  • Focal cortical dysplasia
  • GABA receptor
  • Human

Fingerprint

Dive into the research topics of 'Impaired maturation of cortical GABAA receptor expression in pediatric epilepsy'. Together they form a unique fingerprint.

Cite this