Slow axonal transport is impaired by intrathecal 2,5-hexanedione

Anterograde axonal transport was studied in a new model of hexacarbon neuropathy, in which neurofilament (NF)-containing giant axonal swellings are induced proximally in the spinal nerve roots of rats by intrathecal injection of 2,5-hexanedione (2,5-HD). Decreased transport velocity of the NF-containing slow component a (SCa) was demonstrated in 2,5-HD-treated animals, in contrast to studies demonstrating increased velocity of SCa in proximal parts of the axon in systemic 2,5-HD intoxication, which causes distal axonal swellings. Other components of anterograde transport were unaffected. In systemic 2,5-HD toxicity, velocity of NF transport increases in the proximal axon, but may decrease distally, where it is difficult to study. Decreased NF transport is likely to be responsible for the formation of axonal swellings, since they occur preterminally rather than at the axon terminal as would be expected if increased NF transport were the cause. Covalent modification of proteins provides a possible mechanism by which 2,5-HD affects axonal transport, and the effect may be facilitatory or inhibitory depending on the level and duration of exposure of the NF to the toxin.