Distal axonopathy does not occur without neurofilament accumulation in gamma-diketone neuropathy: comparative studies of normal and neurofilament-deficient quail.

The neurotoxic effects caused by chronic exposure to 2,5-hexanedione (2,5-HD) were investigated in normal and neurofilament (NF)-deficient quail (Quv strain). These quail were given 175 mg/kg per day of 2,5-HD intraperitoneally for 24 weeks. Five of nine normal quail showed clumsy gait. They had NF-rich axonal swellings in the distal parts of the peripheral nerves, ventral and lateral funiculus of the cervical cord, and cerebellar peduncles. Axonal degeneration consisting of accumulation of mitochondria, vesicles, microtubules and dense bodies was found distal to the axonal swellings. Testicular atrophy appeared in two normal quail. In contrast, four of nine Quv quail showed systemic tonic convulsion, and died of respiratory paralysis within 6 days. No significant changes in the nervous system or testis of these four dead Quv quail. The five other Quv quail survived and did not show any neurological signs. Again, no significant changes were detected in the nervous system or testis of the surviving Quv quail. The present study revealed that distal axonal degeneration did not occur without NF accumulation. These results suggest that NF accumulation is an essential factor in the development of distal axonopathy in gamma-diketone neuropathy.