IMPAIRED NEUROGENESIS BY METHYLAZOXYMETHANOL IN NEWBORN RATS RESULTS IN TRANSIENT REDUCTION OF ORNITHINE DECARBOXYLASE AND POLYAMINES IN THE CEREBELLUM, BUT NOT IN THE OLFACTORY BULBS

Polyamines and the key enzyme for their biosynthesis, ornithine decarb oxylase (ODC) play an important role in the control of neuronal prolif eration and differentiation. Exposure to agents that interfere with no rmal cell maturation is expected to result in alteration of neuronal O DC developmental pattern. We have administered to newborn rats, about 6 and 30 hr after birth, 20 mg/kg of methylazoxymethanol acetate (MAM) , an agent able to selectively kill dividing cells and we have evaluat ed ODC activity and polyamine levels in the cerebellum and ODC activit y in the olfactory bulbs at various developmental stages starting from postnatal day 4 (PD 4) until PD 28. Cerebellar weight decreased by 22 -50% at the different developmental stages in MAM-treated animals. A d ecline in OD C specific activity was observed at PD 4 and a decrease o f putrescine levels at PD 4 and PD 6 in the cerebellum. At PD 10, howe ver, both ODC activity and putrescine level were increased in MAM-trea ted animals. Spermidine levels were never affected by the treatment, w hile spermine was significantly decreased at PD 6 and PD 8. These resu lts demonstrate that altered ontogenetic patterns of ODC activity and polyamine levels are the consequence of disturbance of the normal proc ess of brain maturation. No significant differences in specific ODC ac tivity were noticed in the olfactory bulbs of MAM-treated rats. This m ay be related to the more widespread time-span of neurogenesis in this region, a fact that is also revealed by the higher ODC activity const itutively expressed at times in which neurogenesis has ended in the re st of the brain.