The retrograde fast component of axonal transport in motor and sensory nerves of the rat during administration of 2,5-hexanedione.

The retrograde and anterograde fast component of axonal transport (rFC and aFC) were examined in rats following intoxication with 2,5-hexanedione (1 g/kg/week) for 2, 4, 6 and 8 weeks. rFC and aFC were measured as accumulations distal and proximal to a double ligature after labeling of protein by injection of [35S]methionine into L5 spinal cord or L5 dorsal root ganglion. Clinical symptoms appeared after an accumulated dose of 6 g/kg of the toxin and was dominated by motor deficiencies. Abnormalities in retrograde build-up appeared earliest in motor nerves after an accumulated dose of 4 g/kg, while the sensory nerves showed a decreased retrograde build-up only after 6 g/kg. In motor nerves retrograde build-up for the short and the long accumulation interval (11.5-17.5 h and 11.5-25.5 h, respectively) was equally depressed, while in sensory nerves the retrograde build-up for the early accumulation interval (10-16 h) was less severely depressed as compared to the late collection interval (10-24 h). These findings point to a decreased amount of rFC, rather than a delay in turn-around. Furthermore, build-up was inversely correlated with the dose of 2,5-hexanedione and was most pronounced in motor nerves (82% vs 52% in motor and sensory nerves, respectively) at the final dose of 8 g/kg. When intoxication was stopped, rats improved in muscle-strength, but still showed atrophy of leg muscles. Coincidently, retrograde transport in motor nerves was normalized for the short accumulation interval, and improved for the longer collection interval, though not completely normalized.