Role of ornithine decarboxylase and the polyamines in nervous system development: a review.

Development of nervous tissue is controlled, in part, by the ornithine decarboxylase (ODC)/polyamine system. Each brain region possesses a unique ontogenetic pattern for ODC, with highest levels of the enzyme associated with periods of most rapid growth. For this reason, perturbation of the ODC profile has proven useful in examinations of teratologic mechanisms and detection of adverse environmental effects during development. More recently, the replication of neuronal cells in developing brain has been shown to require the maintenance of polyamine levels and consequently, depletion of polyamines by alpha-difluoromethylornithine (DFMO, an ODC inhibitor) arrests brain cell maturation. DFMO also interferes with neuronal migration, axonogenesis and synaptogenesis, leading to disruption of the cytoarchitectural organization of brain structures: these results imply a similarly important role for polyamines in post-replicative events. Indeed, [3H]DFMO-autoradiographic localization of ODC in developing cerebellar lamina indicates high levels of activity associated with neuropil, areas of axonal outgrowth, and post-mitotic granule cells. Axonal outgrowth during regeneration after nerve damage in the mature nervous system may display some of the same characteristics as in developing neurons, suggesting that the two processes share common polyamine-dependent mechanisms.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology