Characterization of carbon disulfide neurotoxicity in C57BL6 mice: Behavioral, morphologic, and molecular effects

Female C57BL6 mice were exposed to 0 or 800 ppm carbon disulfide (CS2). 6 h /d, 5 d/wk for 20 weeks. The neurologic function of all mice was assessed o nce at the end of exposures using a functional observational battery. Gener al health effects included a decrease in body weight gain, piloerection, hu nched body posture, and ptosis. Treatment-related effects included altered gait (uncoordinated placement of hind limbs and ataxia) and impaired functi on on an inverted screen test. In addition, rearing and locomotor movement were decreased in treated mice. Focal to multifocal axonal swelling was see n predominantly in the muscular branch of the posterior tibial nerve, and o ccasionally giant axonal swelling was detected in the lumbar segment of the spinal cord. Electron microscopic examination revealed swollen axons with massive accumulation of neurofilament proteins within the axoplasm. Covalen t crosslinking of erythrocyte spectrin (surrogate protein to neurofilament protein) was demonstrated in mice exposed to CS2 but not in mice receiving filtered air. These data provide supportive evidence that covalent cross-li nking of neurofilament proteins is a significant feature of the axonal swel lings in mice produced by inhalation exposure to CS2.