Regional variations in spermine levels in the developing rat brain following exposure to lead

Abstract

Polyamines are ubiquitous compounds involved in growth and differentiation, and ornithine decarboxylase (ODC), is their rate-limiting enzyme. In an effort to examine whether changes in ODC enzyme activity are reflected in alterations in the availability of polyamines, levels of the more stable end-product spermine, were examined following exposure to lead (Pb). Rats were lactationally exposed to 0.2% Pb-acetate from birth to weaning. At postnatal days 3, 5, 10, 15, and 20, pups were sacrificed, and spermine was extracted from their brain tissue and the extracts were analyzed by high-performance liquid chromatography coupled with a fluorescence detector. Basal spermine levels in the cerebellum were found to be higher than those in the neocortex, and exhibited a characteristic developmental profile. In Pb-exposed animals, spermine levels were attenuated in both brain regions, however, there was a rebound in cerebellar levels during the third week after birth. While basal spermine levels are in concert with reported patterns of ODC activity, they depart from each other following a toxic challenge to the cerebellum. This study suggest that developmental polyamine levels are not necessarily a direct translation of ODC activity and that modulations in their biosynthesis depend on regional stages of growth.