Dexamethasone induces apoptosis of progenitor cells in the subventricular zone and dentate gyrus of developing rat brain

The use of dexamethasone in premature infants to prevent and/or treat bronchopulmonary dysplasia adversely affects neurocognitive development and is associated with cerebral palsy. The underlying mechanisms of these effects are multifactorial and likely include apoptosis. The objective of this study was to confirm whether dexamethasone causes apoptosis in different regions of the developing rat brain. On postnatal day 2, pups in each litter were randomly divided into the dexamethasone-treated (n = 91) or vehicle-treated (n = 92) groups. Rat pups in the dexamethasone group received tapering doses of dexamethasone on postnatal days 3-6 (0.5, 0.25, 0.125, and 0.06 mg/kg/day, respectively). Dexamethasone treatment significantly decreased the gain of body and brain weight and increased brain caspase-3 activity, DNA fragments, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and cleaved caspse-3-positive cells at 24 hr after treatment. Dexamethasone increased cleaved caspse-3-positive cells in the cortex, thalamus, hippocampus, cerebellum, dentate gyrus, and subventricular zone. Double-immunofluorescence studies show that progenitor cells in the subventricular zone and dentate gyrus preferentially undergo apoptosis following dexamethasone exposure. These results indicate that dexamethasone-induced apoptosis in immature cells in developing brain is one of the mechanisms of its neurodegenerative effects in newborn rats.