Mitochondrial complex I inhibition produces selective damage to hippocampal subfield CA1 in organotypic slice cultures.
The effects of mitochondrial respiratory chain inhibitors and the excitotoxin N-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 I 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 micro M Rotenone caused greater cell death in hippocampal subfield CA1 than CA3. Exposure of hippocampal slice cultures to 10 micro M 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.
Xu
Guangping
G
Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA.
Perez-Pinzon
Miguel A
MA
Sick
Thomas J
TJ
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology; D016202:N-Methylaspartate / Q000494:pharmacology; D009574:Nitro Compounds; D009924:Organ Culture Techniques; D011422:Propionates / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology
D009574:Nitro Compounds; D011422:Propionates; D012402:Rotenone; D016202:N-Methylaspartate; D042967:Electron Transport Complex I; C015392:3-nitropropionic acid; D015655:1-Methyl-4-phenylpyridinium