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Abstract
Objective: Focal cortical dysplasia is characterized by disorganized cortical lamination, dysplastic and heterotopic neurons, and an association with epilepsy. The contribution that dysplastic and heterotopic neurons make to epileptogenesis in focal cortical dysplasia is unknown and the phenotype of these cells may be distinct. The authors hypothesized that the expression of genes encoding glutamatergic (glutamate [GluR] and N-methyl-d-aspartate NMDA receptors [NR]) and γ-aminobutyric acid A receptor (GABAAR) subunits is distinct in dysplastic and heterotopic neurons and that changes in receptor gene expression could be defined in a cell-specific pattern.
Methods: Single immunohistochemically labeled dysplastic and heterotopic neurons were microdissected from human focal cortical dysplasia specimens obtained during epilepsy surgery. Pyramidal neurons were microdissected from postmortem control cortex and from temporal cortex without dysplasia resected during temporal lobectomy. Poly (A) messenger RNA (mRNA) from single neurons was amplified, radiolabeled, and used to probe complementary DNA (cDNA) arrays containing GluR1–6, NR1A,1B, NR2A–D, and GABAARα1–6, and -Rβ1–3 subunit cDNAs. The relative hybridization intensities of each mRNA-cDNA hybrid were quantified by phosphorimaging.
Results: GluR, NR, and GABAAR subunit mRNA expression did not differ between control neurons and nondysplastic epilepsy specimens. Expression of GluR4, NR2B, and NR2C subunit mRNA was increased, and NR2A and GABAARβ1 subunit mRNA was decreased in dysplastic compared with pyramidal and heterotopic neurons. In contrast, GABAARα1, -Rα2, and -Rβ2 as well as GluR1 mRNA levels were reduced in both dysplastic and heterotopic neurons.
Conclusions: Differential expression of GluR, NR, and GABAAR mRNA in dysplastic and heterotopic neurons demonstrates cell specific gene transcription changes in focal cortical dysplasia. These results suggest that dysplastic and heterotopic neurons may be pharmacologically distinct and make differential contributions epileptogenesis in focal cortical dysplasia.
- Received July 27, 2000.
- Accepted in final form December 16, 2000.
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- Reply to Roesler et al.
- Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia
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