Abstract |
Measurements of neuron-specific (neurotypic) and glia-specific (fliotypic) proteins were used to characterize the toxic effects of TET on the developing CNS. Six proteins, each of which is associated with specific aspects of neuronal and glial development, were evaluated as follows: (1) NF-200, an intermediate filament protein of the neuronal cytoskeleton; (2) synapsin I, a synapse-specific, synaptic vesicle localized protein;(3) p38, another synaptic-vesicle localized protein; (4) MBP, a protein unique to myelin-forming oligodendroglia; (5) GFAP, the intermediate filament protein of astrocytes; and (6) beta-tubulin, a constituent primarily of neuronal microtubules. The amount of each protein in homogenates of hippocampus, forebrain and cerebellum, brain regions with different developmental profiles, was determined by RIA. TET (3 or 6 mg/kg, i.p.) on postnatal day 5 caused permanent dose- and region-dependent decrements in brain weight, with the hippocampus being the most affected. The effects were not associated with light microscopic evidence of cytopathology but were accompanied by large dose-, time- and region-dependent alterations in all neurotypic and gliotypic proteins evaluated. |