Relationships between neuronal death and the cellular redox status. Focus on the developing nervous system

During the development of the nervous system, a large number of neurons are eliminated through naturally occurring neuronal death. Many morphological and biochemical properties of such dying neurons are reminiscent of apoptos is, a type of death involving the action of genetically-programmed events b ut also epigenetic phenomena including oxidative stress. The following review contains three parts focusing respectively on basic kn owledge of neuronal death and redox regulation, the mechanisms involved in neuronal death which are ordered in three sequential phases, and on the com plex relations between neuronal fate and the redox status. Finally, we point out that oxidants are not always detrimental for neuronal survival. On the one hand, dying neurons often display signs of oxidative stress, including an elevation of their intracellular concentration of free radicals. Antioxidants may reduce the extent of neuronal death, suggesting a causal i mplication of free radicals in the death-process. On the other hand, at hig h concentrations antioxidants may lose their protective effects on developi ng neurons, and a non-lethal oxidative stress may potentiate the protective effects of other agents. These data suggest that free radicals; perhaps through their effects on cel lular signalling pathways, may have positive effects on neuronal survival, provided that their intraneuronal concentrations are maintained at low leve ls. Much evidence suggests that the neuronal redox status must be maintained wi thin a narrow range of values compatible with survival. Antioxidants may pr otect neurons subjected to an oxidative stress following axotomy or trophic factor-deprivation; but excessive reduction may become equally detrimental for neurons. (C) 1999 Elsevier Science Ltd. All rights reserved.