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 decarboxylase (ODC) play an important role in the control of neuronal proliferation and differentiation. Exposure to agents that interfere with normal cell maturation is expected to result in alteration of neuronal ODC 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 evaluated ODC activity and polyamine levels in the cerebellum and ODC activity 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 decline in ODC specific activity was observed at PD 4 and a decrease of putrescine levels at PD 4 and PD 6 in the cerebellum. At PD 10, however, both ODC activity and putrescine level were increased in MAM-treated animals. Spermidine levels were never affected by the treatment, while spermine was significantly decreased at PD 6 and PD 8. These results demonstrate that altered ontogenetic patterns of ODC activity and polyamine levels are the consequence of disturbance of the normal process of brain maturation. No significant differences in specific ODC activity were noticed in the olfactory bulbs of MAM-treated rats. This may be related to the more widespread time-span of neurogenesis in this region, a fact that is also revealed by the higher ODC activity constitutively expressed at times in which neurogenesis has ended in the rest of the brain.
Facchinetti
F
F
Department of Biology, University of Bologna, Italy.
Ciani
E
E
Sparapani
M
M
Barnabei
O
O
Contestabile
A
A
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development*; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D009830:Olfactory Bulb / Q000187:drug effects / Q000254:growth & development*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D011073:Polyamines; D008746:Methylazoxymethanol Acetate; D009955:Ornithine Decarboxylase; C030667:methylazoxymethanol