DECREASED LEVELS OF THE HIGH-MOLECULAR-WEIGHT SUBUNIT OF NEUROFILAMENTS AND ACCELERATED NEUROFILAMENT TRANSPORT DURING THE RECOVERY PHASE OF 2,5-HEXANEDIONE EXPOSURE

The neurotoxicant 2,5-hexanedione (HD) causes the accumulation of neur ofilaments in the distal axon and an acceleration of neurofilament tra nsport proximal to the site of their accumulation. It has been propose d that the acceleration of transport is due to the direct reaction of HD with neurofilament proteins and, conversely, that this acceleration is a secondary response of the axon to injury. The objective of this study was to determine whether the response of axons to HD intoxicatio n includes acceleration of neurofilament transport. Pulse labeling was used to analyze neurofilament transport in age-matched rats exposed t o HD or PBS. The animals receiving HD were exposed either throughout t he period of radiolabel transport, or prior to the pulse labeling of n eurofilament proteins. If acceleration of the rate of neurofilament tr ansport was due to the direct reaction of HD with proteins, then neuro filaments synthesized after the exposure period should travel at contr ol rates, since these proteins would not have been exposed to the toxi cant. After 28 days of transport, optic nerve proteins were examined u sing SDS-PAGE, fluorography, and computerized densitometry. In both HD -treated groups, neurofilament transport was accelerated relative to a ge-matched control animals. In addition, the amount of NFH was decreas ed relative to other neurofilament subunits. The combination of accele rated transport and a diminished proportion of NFH is similar to the o bservations of neurofilament axonal transport during growth and develo pment. These observations suggest that this persistent, secondary effe ct is a reparative response to injury that recapitulates axonal growth and development. (C) 1993 Wiley-Liss, Inc.