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Alternatives to Laboratory Animals - ATLA

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5´-Nucleotidase Activity and Galactolipid Accumulation in Triethyllead-exposed Glial Cell Cultures

Inger K. Grundt, Marvelyn Rise and Harald Nyland

The developing nervous system is vulnerable to heavy metal exposure, which can cause alterations in neuronal and glial cells in the brain. Thus, heavy metals such as mercury and lead reduce myelin galactocerebroside (GalC) synthesis, and increase the ratio of non-hydroxylated fatty acids to hydroxylated fatty acids (GalC-N:GalC-OH) in the GalC molecules in newborn rats. This study investigated the effect of lead on the expression of myelin components by the myelin-forming oligodendroglial cells (OG) in vitro. Primary cultures of mixed glial cells from brains of newborn rats were continuously exposed to triethyllead (TEL; 1nM, 10nM, 50nM and 100nM) for 3 weeks, one week after seeding. The first morphological alteration observed was an increased proliferation of OG in cultures exposed to 10nM TEL. Biochemical analyses showed up-regulation of the enzymes, 2´3´-cyclic nucleotide 3´-phosphodiesterase and 5´-nucleotidase. GalC synthesis was also stimulated, and the ratio GalC-N:GalC-OH was reduced. The results indicate that TEL stimulates the differentiation and maturation of OG in cultures, which suggests that the alterations induced by heavy metals in newborn rats are not due to interference with the OG maturation.