Mechanisms and modulation of neural cell damage induced by oxidative stress

Oxidative stress has been linked to several neurodegenerative disorders characterized by neuronal death. Apoptosis and necrosis are the two major forms of cell death that have been described in the nervous system, and stimuli inducing oxidative stress can cause both types of death, depending on the intensity and the duration of the insult. In the present article, we report on a series of studies from our laboratory describing the intracellular pathways activated by oxidative stress in differentiated neurons, such as cerebellar granule cells, and neural stem cells. Using in vitro/ ex vivo experimental models, we have investigated whether the susceptibility to injuries can be affected by the occurrence of potential insults taking place during development. We have found that prenatal exposure to high levels of glucocorticoids renders neural cells, including stem cells, more sensitive to oxidative stress damage. Similar effects were seen after in utero exposure to methylmercury. The analysis of behavior has proven to be a sensitive tool to detect mild alterations induced by early stimuli that increase susceptibility to oxidative stress. Our findings contribute to the understanding of how early events may have long-term consequences by modifying intracellular processes that predispose the affected cells to dysfunction, which can be unmasked or worsen by subsequent exposure to further injuries. (C) 2007 Elsevier Inc. All rights reserved.