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

[en] 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

Disciplines :

Genetics & genetic processes
Biochemistry, biophysics & molecular biology

Author, co-author :

Molinaro, P.; Federico II University of Naples, 80131 Naples, Italy > Division of Pharmacology, Department of Neuroscience, School of Medicine

Cuomo, O.; Federico II University of Naples, 80131 Naples, Italy > Division of Pharmacology, Department of Neuroscience, School of Medicine

Pignataro, G.; Federico II University of Naples, 80131 Naples, Italy > Division of Pharmacology, Department of Neuroscience, School of Medicine

Boscia, F.; Federico II University of Naples, 80131 Naples, Italy > Division of Pharmacology, Department of Neuroscience, School of Medicine

Sirabella, R.; Federico II University of Naples, 80131 Naples, Italy > Division of Pharmacology, Department of Neuroscience, School of Medicine

Pannaccione, A.; Federico II University of Naples, 80131 Naples, Italy > Division of Pharmacology, Department of Neuroscience, School of Medicine

Secundo, A.; Federico II University of Naples, 80131 Naples, Italy > Division of Pharmacology, Department of Neuroscience, School of Medicine

Scorziello, A.; Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, 80131 Naples, Italy

Adornetto, A.; Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, 80131 Naples, Italy

Gala, R.; Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, 80131 Naples, Italy

More authors (6 more)

Language :

English

Title :

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

Publication date :

2008

Journal title :

Journal of Neuroscience

ISSN :

0270-6474

eISSN :

1529-2401

Publisher :

Society for Neuroscience, Washington, United States - District of Columbia

Volume :

Pages :

1179-1184

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 19 January 2010

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