Disruption of rat forebrain development by glucocorticoids: critical perinatal periods for effects on neural cell acquisition and on cell signaling cascades mediating noradrenergic and cholinergic neurotransmitter/neurotrophic responses.

摘要: Glucocorticoids are the consensus treatment for prevention of respiratory distress in preterm infants, but there is evidence increased incidence neurodevelopmental disorders as a result their administration. We administered dexamethasone (Dex) to developing rats at doses below or within range those used clinically, evaluating effects on forebrain development with exposure three different stages: gestational days 17-19, postnatal 1-3, 7-9. At 24 h after last dose, we evaluated biomarkers neural cell acquisition and growth, synaptic development, neurotransmitter receptor expression, signaling mediated by adenylyl cyclase (AC). Dex impaired cells, peak effect when given immediate period. In association this defect, also elicited biphasic cholinergic presynaptic promoting maturation dose (0.05 mg/kg) well therapeutically, whereas was diminished lost were 0.2 0.8 mg/kg. postnatally disrupted expression adrenergic receptors known participate neurotrophic modeling brain evoked massive induction AC activity. As consequence, disparate inputs all produced cyclic AMP overproduction, likely contributor patterns replication, differentiation, apoptosis. Superimposed heterologous induction, specific receptor-mediated signals. These results indicate that, during critical developmental period, administration leads widespread interference contributing eventual, adverse neurobehavioral outcomes.