Fetal dexamethasone exposure sensitizes neonatal rat brain to hypoxia: effects on protein and DNA synthesis.
Fetal exposure to glucocorticoids is known to produce long-term alterations in cell development within the central nervous system. The current study examines whether some of the adverse effects of prenatal dexamethasone treatment on brain development represent sensitization to hypoxia-induced damage. Pregnant rats were given 0.2 or 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19 and their offspring were challenged by exposure to 7% O2 on postnatal days 1 and 8. In control rats at 1 day of age, hypoxia evoked an acute decrease in protein synthesis, assessed by [3H]leucine incorporation, in both the midbrain + brainstem and forebrain. The decrease was also seen in animals receiving the low dose of dexamethasone, but was of smaller magnitude in the midbrain + brainstem than in the control cohort. At the higher dose of dexamethasone, hypoxia failed to evoke a decrease in protein synthesis; instead, protein synthesis was significantly increased. By 8 days of age, the animals receiving the lower dose of dexamethasone also displayed the anomalous increment in [3H]leucine incorporation during hypoxic challenge, whereas the effect in the high dose group was less notable. Similarly, parallel examination of incorporation of [3H]thymidine into DNA on postnatal day 1 indicated that control animals would reduce their macromolecule synthetic rate in a hypoxic environment, but that animals exposed to the high dose of dexamethasone would not; unlike the case with protein synthesis, however, the dexamethasone group never showed an increase in DNA synthesis during hypoxia. By 8 days of age, the interaction between the high dose of dexamethasone and hypoxia was no longer apparent for DNA synthesis.2
Carlos
R Q
RQ
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Seidler
F J
FJ
Slotkin
T A
TA
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D004247:DNA / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007930:Leucine / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D009419:Nerve Tissue Proteins; D003907:Dexamethasone; D004247:DNA; D007930:Leucine; D013936:Thymidine