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Mitochondrial complex I inhibition produces selective damage to hippocampal subfield CA1 in organotypic slice cultures

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Abstract

The effects of mitochondrial respiratory chain inhibitors and the excitotoxinN-methyl-D-aspartate (NMDA) on cell death in hippocampal subfields CA1 and CA3 were examined in hippocampal organotypic slice cultures. Slice cultures, 2–3 week old, were exposed for 1 h to either the Complex 1 inhibitors, rotenone or 1-methyl-4-phenylpyridium (MPP+), the Complex II inhibitor 3-nitropropionic acid (3-NP), or the excitotoxin NMDA. Cell death was examined 24 and 48 h following treatment, by measuring propidium iodide (PI) fluorescence. Treatment with 1 μM rotenone caused greater cell death in hippocampal subfield CA1 than CA3. Exposure of hippocampal slice cultures to 10 μM rotenone, to MPP+ or to NMDA resulted in damage to both CA1 and CA3 subfields. 3-NP produced little damage in either subfield. The data suggest that mitochondrial complex I inhibition can produce selective cell damage in hippocampus and in this regard is similar to that observed following hypoxia/ischemia.

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Authors and Affiliations

  1. Department of Neurology, University of Miami School of Medicine, 33101, Miami, FL, USA

    Guangping Xu, Miguel A. Perez-Pinzon & Thomas J. Sick

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  1. Guangping Xu
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  2. Miguel A. Perez-Pinzon
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  3. Thomas J. Sick
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Correspondence to Thomas J. Sick.

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Xu, G., Perez-Pinzon, M.A. & Sick, T.J. Mitochondrial complex I inhibition produces selective damage to hippocampal subfield CA1 in organotypic slice cultures. neurotox res 5, 529–537 (2003). https://doi.org/10.1007/BF03033163

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  • DOI: https://doi.org/10.1007/BF03033163

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