Article (Scientific journals)
NCX3 knockout mice exhibit increased hippocampal CA1 and CA2 neuronal damage compared to wild-type mice following global cerebral ischemia
Jeffs, G. J.; Meloni, B.; Sokolow, S. et al.
2008In Experimental Neurology, 210, p. 268-273
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Keywords :
Global cerebral ischemia; Na+/Ca2+ exchanger; Neuroprotection; Knockout mice; CA neurons
Abstract :
[en] There is uncertainty as to whether the plasma membrane Na(+)/Ca(2+)exchanger (NCX) has a neuroprotective or neurodamaging role following cerebral ischemia. To address this issue we compared hippocampal neuronal injury in NCX3 knockout mice (Ncx3(-/-)) and wild-type mice (Ncx3(+/+)) following global cerebral ischemia. Using a bilateral common carotid artery occlusion (BCCAO) model of global ischemia we subjected NCX3 knockout and wild-type mice to 17 and 15 minutes of ischemia. Following the 17 minute period of ischemia, wild-type mice exhibited approximately 80% CA1 neuronal loss and approximately 40% CA2 neuronal loss. In contrast, NCX3 knockout mice displayed >95% CA1 neuronal loss and approximately 95% CA2 neuronal loss. Following the 15 minute period of ischemia, wild-type mice did not exhibit any significant hippocampal neuronal loss. In contrast, NCX3 knockout mice displayed approximately 45% CA1 neuronal loss and approximately 25% CA2 neuronal loss. The results clearly demonstrate that mice deficient in the NCX3 protein are more susceptible to global cerebral ischemia than wild-type mice. Our findings suggest NCX3 has a positive role in maintaining neuronal intracellular calcium homeostasis following ischemia, and that when exchanger function is compromised neurons are more susceptible to calcium deregulation and cell death
Disciplines :
Biochemistry, biophysics & molecular biology
Genetics & genetic processes
Author, co-author :
Jeffs, G. J.;  Centre for Neuromuscular and Neurological Disorders/University of Western Australia, Australia
Meloni, B.;  Centre for Neuromuscular and Neurological Disorders/University of Western Australia, Australia
Sokolow, S.;  University of California at Los Angeles, School of Nursing, Los Angeles, CA, USA
Herschuelz, A.;  Université Libre de Bruxelles - ULB > Laboratory of Pharmacology and Therapeutics
Schurmans, Stéphane  ;  Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie métabolique vétérinaire
Knuckey, N. W.;  Centre for Neuromuscular and Neurological Disorders/University of Western Australia, Australia
Language :
English
Title :
NCX3 knockout mice exhibit increased hippocampal CA1 and CA2 neuronal damage compared to wild-type mice following global cerebral ischemia
Publication date :
2008
Journal title :
Experimental Neurology
ISSN :
0014-4886
eISSN :
1090-2430
Publisher :
Academic Press, Orlando, United States - Florida
Volume :
210
Pages :
268-273
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 19 January 2010

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