Article (Scientific journals)
Targeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage
Molinaro, P.; Cuomo, O.; Pignataro, G. et al.
2008In Journal of Neuroscience, 28, p. 1179-1184
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Keywords :
NCX; MCAO; cerebral ischemia; sodium calcium exchanger; OGD; organotypic hippocampal cultures
Abstract :
[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
Viggiona, D.;  Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, 80131 Naples, Italy
Sokolow, S.;  Federico II University of Naples, 80131 Naples, Italy
Herchuelz, A.;  Federico II University of Naples, 80131 Naples, Italy
Schurmans, Stéphane  ;  Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire
Di Renzo, G.;  Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, 80131 Naples, Italy
Annunziato, L.;  Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, 80131 Naples, Italy
More authors (6 more) Less
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 :
28
Pages :
1179-1184
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 19 January 2010

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