ORNITHINE DECARBOXYLASE ACTIVITY IN FETAL AND NEWBORN RAT-BRAIN - RESPONSES TO HYPOXIC AND CARBON-MONOXIDE HYPOXIA

In response to acute maternal hypoxia, ornithine decarboxylase (ODC) a ctivity increased significantly in fetal rat brain, peaking at 4 h. Th is was associated with increased ODC mRNA and elevated polyamine conce ntrations. To correlate this response with development, we measured OD C activity in the rat from gestational day E 17 to postnatal day P 10. We also examined to what extent hypoxia induces increased ODC activit y in adult rat brains and whether the response to chronic hypoxia diff ered from that to acute hypoxia. To test the hypothesis that this incr eased activity is due to hypoxic hypoxia per se, we subjected pregnant dams to inspired carbon monoxide concentrations ranging from 150 to 1 000 ppm and assayed ODC activity in the fetal brain 4 h later. In the fetus, ODC activity was elevated on E 17 in the cerebrum and cerebellu m. It declined gradually to about one-tenth E 17 levels by E 21 and re mained low thereafter except for a postnatal elevation in the cerebell um on P 3. In response to 10.5% O2, in the 3-day-old rat, ODC activity peaked between 2 and 3 h of hypoxia, increasing 3-fold in the hippoca mpus and 2-fold in cerebellum. Similar increases were seen in the hypo xic adult rat brain. In inspired oxygen dose-response studies, exposur e of P 3 rat pups to 13.25% O2 for 2.5 h produced a 1.5-fold increase in ODC activity; 10.5% O2 produced a 2-3-fold increase while in respon se to 9% O2, ODC activity remained at baseline levels. With maternal C O-hypoxia, ODC activity increased in the fetal brain at 4 h, as seen w ith hypoxic-hypoxia. For example, in hippocampus, ODC activity doubled at 500 ppm and tripled at 600 ppm. We conclude: (1) apparently, the a bility to respond thus is not lost as the animal ages and may represen t an important cellular response to acute hypoxia; (2) the increase in hypoxic-induced ODC activity is relative to the already elevated acti vity seen from E 17 to E 20; a vast reserve for the induction of fetal ODC activity probably exists and may indicate the importance of this enzyme during this time frame for differentiation and growth promotion ; and (3) the CO-hypoxia studies suggest that some aspects of the cell ular responses to CO- and hypoxic-hypoxia are similar.