TY - JOUR
T1 - Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage
AU - Molinaro, Pasquale
AU - Cuomo, Ornella
AU - Pignataro, Giuseppe
AU - Boscia, Francesca
AU - Sirabella, Rossana
AU - Pannaccione, Anna
AU - Secondo, Agnese
AU - Scorziello, Antonella
AU - Adornetto, Annagrazia
AU - Gala, Rosaria
AU - Viggiano, Davide
AU - Sokolow, Sophie
AU - Herchuelz, Andre
AU - Schurmans, Stèphane
AU - Di Renzo, Gianfranco
AU - Annunziato, Lucio
PY - 2008/1/30
Y1 - 2008/1/30
N2 - 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.
AB - 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.
KW - Cerebral ischemia
KW - MCAO
KW - NCX
KW - OGD
KW - Organotypic hippocampal cultures
KW - Sodium calcium exchanger
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U2 - 10.1523/JNEUROSCI.4671-07.2008
DO - 10.1523/JNEUROSCI.4671-07.2008
M3 - Article
C2 - 18234895
AN - SCOPUS:38749106974
VL - 28
SP - 1179
EP - 1184
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 5
ER -