Acute exposure of the neonatal rat to triethyltin results in persistent changes in neurotypic and gliotypic proteins.
Measurements of neuron-specific (neurotypic) and glia-specific (gliotypic) proteins were used to characterize the toxic effects of triethyltin (TET) on the developing central nervous system. Six proteins, each of which is associated with specific aspects of neuronal and glial development, were evaluated as follows: 1) neurofilament-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) myelin basic protein, a protein unique to myelin-forming oligodendroglia; 5) glial fibrillary acidic protein, 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 radioimmunoassay. After a single administration on postnatal day 5, TET (3 or 6 mg/kg i.p.) caused permanent dose- and region-dependent decrements in brain weight, with the hippocampus being the most affected. These 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. On a per structure (total) basis, TET caused permanent decreases in most neurotypic and gliotypic proteins in all areas. On a per milligram of tissue protein (concentration) basis, changes in specific proteins also were observed in all regions but were most prevalent in hippocampus and cerebellum. In hippocampus and cerebellum, decrements in the concentration of neurotypic and gliotypic proteins were observed in the absence of TET-induced decreases in the weights of these structures. The data indicate that 1) neonatal exposure to TET causes permanent deficits in neuronal as well as glial development, 2) the effects of TET are region-dependent but do not appear to be related to region-dependent stages in development and 3) assays of neurotypic and gliotypic proteins may be used to characterize the temporal and regional patterns of neuronal and glial responses to toxic exposures of the developing central nervous system.
O'Callaghan
J P
JP
Neurotoxicology Division U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
Miller
D B
DB
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000187:drug effects; D007163:Immunosorbent Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014267:Triethyltin Compounds / Q000633:toxicity*
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D014220:Trialkyltin Compounds; D014267:Triethyltin Compounds; C031575:triethyltin