Fetal dexamethasone exposure alters macromolecular characteristics of rat brain development: a critical period for regionally selective alterations?
Fetal glucocorticoid exposure retards postnatal growth and evokes abnormalities of nervous system structure and function. To examine the underlying mechanisms, we administered 0.2 or 0.8 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19 and assessed brain region cell development with indices of DNA content (total cell numbers), DNA concentration (cell packing density), and protein/DNA ratio (relative cell size). Dexamethasone evoked deficits of pup body and brain region weights, but the brain regions displayed growth-sparing associated initially with preservation of cell numbers (normal or elevated DNA content and concentration), at the expense of relative cell size (decreased protein/DNA). Subsequently, brain cell acquisition lagged behind that of controls, with deficits in DNA and elevations of protein/DNA. In midbrain + brainstem and in cerebellum, cell markers returned to normal by weaning. However, the forebrain showed persistent elevations of DNA and reduced protein/DNA, indicative of replacement of neurons with glia. Because the treatment period coincided with the timing of neuronal cell replication in the forebrain, but not in the other regions, these results suggest that the critical period for lasting deficits of dexamethasone coincides with the peak of neuronal mitosis.
Carlos
R Q
RQ
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Seidler
F J
FJ
Slotkin
T A
TA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; 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; D013936:Thymidine