NEURON-SPECIFIC PHOSPHOPROTEINS AS BIOCHEMICAL INDICATORS OF NEUROTOXICITY - EFFECTS OF ACUTE ADMINISTRATION OF TRIMETHYLTIN TO THE ADULT-RAT

Abstract

The cytoarchitecture of the adult CNS is expressed by proteins specific to individual cell types. A subclass of these proteins, the neuron-specific phosphoproteins, was examined after the administration of trimethyltin (TMT), a neurotoxicant which preferentially damages neurons in limbic structures. After acute administration of TMT (0.0-9.0 mg/kg i.v.), effects on neuronal phosphoproteins were examined by 3 separate techniques: endogenous phosphorylation of total synaptic membrane proteins; radiometric assay or synapsin I, a neuron-specific phosphoprotein associated with synaptic vesicles; and radioimmunoassay of synapsin I and protein III, another synapse specific, synaptic vesicle-localized phosphoprotein. All 3 procedures gave similar results. TMT caused dose- and time-dependent decreases in hippocampal phosphoproteins. These effects were large in magnitude and were still evident 14 wk after exposure to TMT. Microdissection of slices of dorsal hippocampus did not reveal significant regional differences in the extent to which TMT affected synapsin I. Phosphoproteins in frontal cortex, unlike those in hippocampus, were not affected by TMT. The findings are consistent with the neuropathological effects of the compound and suggest that neuron-specific phosphoproteins may be useful biochemical indicators of neurotoxicity.