Pyramidal cell responses to γ-aminobutyric acid differ in type I and Type II cortical dysplasia

Mental Retardation Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Journal of Neuroscience Research (Impact Factor: 2.59). 11/2008; 86(14):3151-62. DOI: 10.1002/jnr.21752
Source: PubMed


Abnormalities in the gamma-aminobutyric acid (GABA)-ergic system could be responsible for seizures in cortical dysplasia (CD). We examined responses of pyramidal neurons to exogenous application of GABA, as well as alterations of GABAergic interneuron number and size in pediatric epilepsy surgery patients with non-CD, type I CD, and type II CD pathologies. We used the dissociated cell preparation for electrophysiology along with immunohistochemistry to identify number and size of GABAergic cells. Pyramidal neurons from type I CD tissue showed increased EC(50) and faster kinetics compared with cells from non-CD and type II CD tissue. Cytomegalic pyramidal neurons showed increased GABA peak currents and decreased peak current densities, longer kinetics, and decreased sensitivity to zolpidem and zinc compared with normal pyramidal cells from non-CD and type I CD. There were fewer but larger glutamic acid decarboxylase (GAD)-containing cells in type II CD tissue with cytomegalic neurons compared with non-CD, type I CD, and type II CD without cytomegalic neurons. In addition, GABA transporters (VGAT and GAT-1) showed increased staining surrounding cytomegalic neurons in type II CD tissue. These results indicate that there are differences in GABA(A) receptor-mediated pyramidal cell responses in type I and type II CD. Alterations in zolpidem and zinc sensitivities also suggest that cytomegalic neurons have altered GABA(A) receptor subunit composition. These findings support the hypothesis that patients with type I and type II CD will respond differently to GABA-mediated antiepileptic drugs and that cytomegalic neurons have features similar to immature neurons with prolonged GABA(A) receptor open channel times.

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    • "The specificity of this antibody for parvalbumin in the rodent brain was described by Felch and Van Hooser (2012). It was also shown to label neurons in cortex of rat and mouse (Salgado et al., 2007; Schmid et al., 2008) and also used in a study of cortical dysplasia in humans (Andr e et al., 2008). "
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    Full-text · Article · Oct 2014 · The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology
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    • "Furthermore, immunocytochemical (ICC) studies have revealed the peculiar aspect of the affected cortex suggesting that, in addition to the structural disarrangement, neurochemical organisation is also disrupted (Spreafico et al., 1998; Garbelli et al., 1999; Tassi et al., 2001). Recent electrophysiological studies performed on dissociated neurons and brain slices obtained from surgical specimens with proven type II FCD have also reported anomalous cellular behaviour (D'Antuono et al., 2004; Cepeda et al., 2007; Andre et al., 2008). These abnormal cytoarchitectural, neurochemical, and electrophysiological characteristics suggest selective morphofunctional alterations in type II FCD that might explain the distinctive ictal and interictal EEG patterns (Tassi et al., 2002; Garbelli et al., 1999; Chassoux et al., 2000). "
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    • "viousstudiesofpediatricepileptictissue(Andreetal.,2004); however,wedidnotdirectlytestforthisinourstudy.Because burstingwasinducedalsointhepresenceofbicuculline,differences inGABAAreceptorsensitivity(Andreetal.,2008)orsubunit compositioncouldalsocontributetothisdifference(Jansenetal., 2008).Thisconclusionwouldbeconsistentwiththehypothesisthat abnormalitiesintheGABAergicandglutamatergic(NMDAreceptor )systemcouldcontributetotheseizuresinCD. "
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