NADPH diaphorase-containing striatal or cortical neurons are resistant to apoptosis.
The small subpopulation of striatal neurons containing nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d, recently identified as nitric oxide synthase, NOS) is selectively spared in Huntington's disease. Previous search for pathogenic mechanisms capable of destroying striatal neurons but sparing NADPH-d(+) cells has identified only NMDA receptor-mediated excitotoxicity. In view of suggestions that neuronal death in Huntington's disease may occur by apoptosis, we examined the vulnerability of NADPH-d(+) neurons to apoptosis. Murine striatal or cortical cultures exposed to serum deprivation developed extensive neuronal apoptosis, but NADPH-d(+) neurons were relatively spared. This sparing was seen when cultures were exposed to several other apoptosis-inducing insults. It was not seen after toxic exposure to H2O2, and it was not blocked by NOS inhibition. The selective resistance of NADPH-d(+) neurons to several forms of apoptosis provides key support for the possibility that apoptosis may contribute to the pathogenesis of Huntington's disease.
Behrens
M I
MI
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Koh
J Y
JY
Muller
M C
MC
Choi
D W
DW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000201:enzymology; D003342:Corpus Striatum / Q000166:cytology* / Q000201:enzymology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D009252:NADPH Dehydrogenase / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009553:Nimodipine / Q000494:pharmacology; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D009574:Nitro Compounds; D011422:Propionates; D011500:Protein Synthesis Inhibitors; D009553:Nimodipine; D003513:Cycloheximide; D009252:NADPH Dehydrogenase; D019311:Staurosporine; C015392:3-nitropropionic acid