Development of polyamine and biogenic amine systems in brains and hearts of neonatal rats given dexamethasone: role of biochemical alterations in cellular maturation for producing deficits in ontogeny of neurotransmitter levels, uptake, storage and turnover.
Excessive levels of glucocorticoids are thought to interfere with synaptic development in the central nervous system. In the present study, dexamethasone given to newborn rats produced deficits in brain growth associated with shifts in the developmental pattern of the ornithine decarboxylase/polyamine system consistent with delays in cellular maturation. The effects on the brain were of smaller magnitude and shorter duration than those on the heart or on general growth and were indicative of "brain sparing." Although some biochemical indices of synaptic development of central noradrenergic systems ([3H]norepinephrine uptake into synaptosomes) were quantitatively deficient on a whole-brain basis, the reductions never exceeded the magnitude of effect on brain weight; for other indices (transmitter levels, [3H]norepinephrine into synaptic vesicles), there were little or no apparent developmental deficits. Thus, the effects of dexamethasone on synaptic development in the brain may not reflect a specific action of glucocorticoids over and above their more general effects on cellular maturation. In contrast to the lack of specific action on biochemical indices of synaptic outgrowth, neonatal dexamethasone did cause alterations in norepinephrine synthesis and turnover in both central and peripheral sympathetic neurons which could contribute to the physiological and behavioral abnormalities associated with glucocorticoid treatment during development.
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000254:growth & development; D009206:Myocardium / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D001679:Biogenic Amines; D018377:Neurotransmitter Agents; D011073:Polyamines; D003907:Dexamethasone