Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage

Pasquale Molinaro, Ornella Cuomo, Giuseppe Pignataro, Francesca Boscia, Rossana Sirabella, Anna Pannaccione, Agnese Secondo, Antonella Scorziello, Annagrazia Adornetto, Rosaria Gala, Davide Viggiano, Sophie Sokolow, Andre Herchuelz, Stèphane Schurmans, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review

Abstract

Na+/Ca+ exchanger 3 (NCX3), one of the three isoforms of the NCX family, is highly expressed in the brain and is involved in the maintenance of intracellular Na+ and Ca2+ homeostasis. Interestingly, whereas the function of NCX3 under physiological conditions has been determined, its role under anoxia is still unknown. To assess NCX3 role in cerebral ischemia, we exposed ncx3-/- mice to transient middle cerebral artery occlusion followed by reperfusion. In addition, to evaluate the effect of ncx3 ablation on neuronal survival, organotypic hippocampal cultures and primary cortical neurons from ncx3-/- mice were subjected to oxygen glucose deprivation (OGD) plus reoxygenation. Here we report that ncx3 gene suppression leads to a worsening of brain damage after focal ischemia and to a massive neuronal death in all the hippocampal fields of organotypic cultures as well as in cortical neurons from ncx3-/- mice exposed to OGD plus reoxygenation. In addition, in ncx3-/- cortical neurons exposed to hypoxia, NCX currents, recorded in the reverse mode of operation, were significantly lower than those detected in ncx3-/-. From these results, NCX3 protein emerges as a new molecular target that may have a potential therapeutic value in modulating cerebral ischemia.

Original languageEnglish
Pages (from-to)1179-1184
Number of pages6
JournalJournal of Neuroscience
Volume28
Issue number5
DOIs
Publication statusPublished - Jan 30 2008

Keywords

  • Cerebral ischemia
  • MCAO
  • NCX
  • OGD
  • Organotypic hippocampal cultures
  • Sodium calcium exchanger

ASJC Scopus subject areas

  • Neuroscience(all)

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