Acute exposure of the neonatal rat to tributyltin results in decreases in biochemical indicators of synaptogenesis and myelinogenesis.
Assays of neuron-localized (neurotypic) and glia-localized (gliotypic) proteins were used to detect and characterize the toxic effects of tributyltin (TBT) on the developing rat central nervous system. Four proteins associated with specific aspects of neuronal and glial development were evaluated: 1) p38, a synaptic vesicle-associated protein; 2) neurofilament 200, an intermediate filament protein of the neuronal cytoskeleton; 3) myelin basic protein, an oligodendroglia and myelin-sheath associated protein; and 4) glial fibrillary acidic protein, an intermediate filament protein of astrocytes. On postnatal days 13, 22 and 60, the amount of each protein in homogenates of cerebellum, forebrain and hippocampus was determined by radioimmunoassay. A single administration of TBT (2, 3 or 4 mg/kg i.p.) on postnatal day 5 caused dose- and region-dependent decreases in brain weight with the cerebellum being most affected. These decrements were not associated with light microscopic evidence of altered brain development (on postnatal day 61) but were accompanied by large dose- and region-dependent decreases in p38 and myelin basic protein. Decrements in both the per tissue (total) and per milligram of tissue protein (concentration) values for these proteins were observed in cerebellum and forebrain; hippocampus was largely unaffected. TBT-induced reductions in p38 and myelin basic protein were seen at dosages that did not affect brain, thymus or body weight. At dosages of TBT that did not affect body weight, reductions in brain weight, p 38 and myelin basic protein did not persist into adulthood. The data indicate that exposure to TBT on postnatal day 5 is toxic to the developing nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Callaghan
J P
JP
Neurotoxicology Division, 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; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D009185:Myelin Proteins / Q000032:analysis; D009186:Myelin Sheath / Q000187:drug effects* / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D013154:Spleen / Q000187:drug effects; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D013950:Thymus Gland / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D005904:Glial Fibrillary Acidic Protein; D009185:Myelin Proteins; D014220:Trialkyltin Compounds; C011559:tributyltin