RT Journal Article
SR Electronic
T1 Targeted Disruption of Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger 3 (NCX3) Gene Leads to a Worsening of Ischemic Brain Damage
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1179
OP 1184
DO 10.1523/JNEUROSCI.4671-07.2008
VO 28
IS 5
A1 Pasquale Molinaro
A1 Ornella Cuomo
A1 Giuseppe Pignataro
A1 Francesca Boscia
A1 Rossana Sirabella
A1 Anna Pannaccione
A1 Agnese Secondo
A1 Antonella Scorziello
A1 Annagrazia Adornetto
A1 Rosaria Gala
A1 Davide Viggiano
A1 Sophie Sokolow
A1 Andre Herchuelz
A1 Stèphane Schurmans
A1 Gianfranco Di Renzo
A1 Lucio Annunziato
YR 2008
UL http://www.jneurosci.org/content/28/5/1179.abstract
AB Na+/Ca2+ 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.