NMDA receptor composition differs among anatomically diverse malformations of cortical development

Adele Finardi, Fabrizio Gardoni, Stefania Bassanini, Giovanni Lasio, Massimo Cossu, Laura Tassi, Claudio Caccia, Franco Taroni, Giorgio LoRusso, Monica Di Luca, Giorgio Battaglia

Research output: Contribution to journalArticle

Abstract

Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.

Original languageEnglish
Pages (from-to)883-893
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume65
Issue number9
DOIs
Publication statusPublished - Sep 2006

Keywords

  • Cerebral malformations
  • Focal cortical dysplasia
  • Glutamatergic synapse
  • Mechanisms of epileptogenesis
  • Periventricular nodular heterotopia
  • Subcortical band heterotopia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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