Journal
NEUROBIOLOGY OF DISEASE
Volume 37, Issue 2, Pages 403-411Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.10.020
Keywords
Calcium; Excitotoxicity; Hippocampal slice cultures; Reactive oxygen species; Zinc; Electron probe microanalysis
Categories
Funding
- NIH
- NINDS
Ask authors/readers for more resources
Hippocampal CA1 pyramidal neurons are selectively vulnerable to ischemia, while adjacent CA3 neurons are relatively resistant. Although glutamate receptor-mediated mitochondrial Ca2+ overload and dysfunction is a major component of ischemia-induced neuronal death, no direct relationship between selective neuronal vulnerability and mitochondrial dysfunction has been demonstrated in intact brain preparations. Here, we show that in organotypic slice cultures NMDA induces much larger Ca2+ elevations in vulnerable CA1 neurons than in resistant CA3. Consequently, CA1 mitochondria exhibit stronger calcium accumulation, more extensive swelling and damage, stronger depolarization of their membrane potential, and a significant increase in ROS generation. NMDA-induced Ca2+ and RCS elevations were abolished in Ca2+-free medium or by NMDAR antagonists, but not by zinc chelation. We conclude that Ca2+ overload-dependent mitochondrial dysfunction is a determining factor in the selective vulnerability of CA1 neurons. Published by Elsevier Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available