There is growing concern that prenatal exposure to excessive glucocorticoids may have deleterious effects on the development of various organs, including the nervous system. This study aimed at evaluating whether prenatal exposure to high levels of glucocorticoids might produce long-term effects on neuronal cell survival. Pregnant rats were injected i.p. with 0.1 mg/kg dexamethasone (DEX) from day 14 postconception, and cerebellar granule cells (CGC) were prepared from 1-week-old rats from DEX-treated and control dams. After 7 days in culture, cells were exposed to H(2)O(2), methylmercury, or colchicine at concentrations known to induce apoptotic cell death. After exposure to H(2)O(2) or methylmercury, both inducing oxidative stress, the number of apoptotic cells was significantly higher in DEX- than in control-CGC. Because mitochondria play a key role in apoptosis, mitochondrial function was investigated, and a decrease in the threshold level of Ca(2+) necessary for induction of mitochondrial permeability transition, in Ca(2+) accumulation rate, and in oxygen consumption was detected in DEX-CGC. Moreover, the activity of the antioxidant enzyme catalase was significantly decreased in DEX-CGC. A similar decrease in catalase activity was observed in cerebellar homogenate from newborn and 40-day-old DEX-rats. In conclusion, these results indicate that prenatal exposure to high levels of glucocorticoids induces long-lasting changes in CGC rendering them more sensitive to oxidative stress. With the increasing use of multiple doses of glucocorticoids in preterm infants, the possibility that prenatal exposure to excess glucocorticoids may lead to long-term neurological consequences becomes a relevant issue.