Motoneuronal death during spinal cord development is mediated by oxidative stress.
The involvement of reactive oxygen species (ROS) in neuronal death has been determined in culture, and in association with several neurodegenerative disorders. We examined whether ROS participate in the cell death observed during spinal cord development. We found that the general pattern of high ROS levels, gene expression for some antioxidant enzymes, and motoneuron death correlated positively along spinal cord development. ROS were reduced in spinal cords cultured in the presence of a synthetic superoxide dismutase and catalase mimetic, with a concomitant reduction in cell death and an increase in the number of motoneurons. The number of motoneurons was higher in spinal cords treated with the antioxidant than in those treated with caspase inhibitors. In general, the increase in motoneuron survival did not correlate with the reduction in cells undergoing DNA degradation in the motoneuronal region. These results suggest that ROS are signaling molecules controlling caspase-dependent and caspase-independent programmed motoneuron death, and support the hypothesis that this mechanism is abnormally turned on in some neurodegenerative disorders and aging.
Sánchez-Carbente
M R
MR
Department of Developmental Genetics and Molecular Physiology, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca Mor. 62210, México.
Castro-Obregón
S
S
Covarrubias
L
L
Narváez
V
V
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D002374:Catalase / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013909:Thorax; D046509:Tissue Culture Techniques
D000975:Antioxidants; D061945:Caspase Inhibitors; C433928:EUK-134; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D012459:Salicylates; D002374:Catalase; D013482:Superoxide Dismutase; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9