αCAMKII and NMDA-receptor subunit expression in epileptogenic cortex from human periventricular nodular heterotopia

Giorgio Battaglia, Silvia Pagliardini, Arianna Ferrario, Fabrizio Gardoni, Laura Tassi, Veronica Setola, Rita Garbelli, Giorgio LoRusso, Roberto Spreafico, Monica Di Luca, Giuliano Avanzini

Research output: Contribution to journalArticle

Abstract

Purpose: Periventricular nodular heterotopia (PNH) is the most common human brain dysgenesis, very frequently characterized by focal drug-resistant epilepsy. To understand the cellular mechanisms underlying its intrinsic hyperexcitability, we investigated the expression of glutamate-receptor subunits and related proteins in four human patients affected by PNH. Methods: PNH was diagnosed by means of magnetic resonance imaging. The epileptogenic area was revealed by depth electrode recordings and removed during epilepsy surgery. Sections from the removed cerebral tissue were analyzed by means of immunocytochemistry (ICC), with antibodies directed against N-methyl-D-aspartate (NMDA)-receptor subunits, the α subunit of the Ca2+/calmodulin-dependent kinase II (αCaMKII), and its active phosphorylated form. Results: The ICC data demonstrated that the subcortical heterotopic nodules were consistently characterized by lower expression of αCaMKII and its activated form. In more pronounced cases (i.e., when the extension of the nodules to the neocortex determined clear layering abnormalities), the heterotopic tissue also was characterized by a decreased expression of NMDA-receptor subunits, which was particularly evident in the dendritic compartment. Conclusions: These data suggest the existence of an alteration of αCaMKII and the NMDA-receptor complex in the epileptogenic brain tissue of human PNH, which may play a role in the basic mechanisms of hyperexcitability associated with this brain dysgenesis.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalEpilepsia
Volume43
Issue numberSUPPL. 5
DOIs
Publication statusPublished - 2002

Keywords

  • αCaMKII
  • Cerebral dysgenesis
  • Epilepsy
  • Glutamate
  • NMDA-receptor complex

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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    Battaglia, G., Pagliardini, S., Ferrario, A., Gardoni, F., Tassi, L., Setola, V., Garbelli, R., LoRusso, G., Spreafico, R., Di Luca, M., & Avanzini, G. (2002). αCAMKII and NMDA-receptor subunit expression in epileptogenic cortex from human periventricular nodular heterotopia. Epilepsia, 43(SUPPL. 5), 209-216. https://doi.org/10.1046/j.1528-1157.43.s.5.38.x