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 neurofilaments in the distal axon and an acceleration of neurofilament transport proximal to the site of their accumulation. It has been proposed 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 to the axon to injury. The objective of this study was to determine whether the response of axons to HD intoxication includes acceleration of neurofilament transport. Pulse labelling was used to analyze neurofilament transport in age-matched rats exposed to HD or PBS. The animals receiving HD were exposed either throughout the period of radiolabel transport, or prior to the pulse labeling of neurofilament proteins. If acceleration of the rate of neurofilament transport was due to the direct reaction of HD with proteins, then neurofilaments synthesized after the exposure period should travel at control rates, since these proteins would not have been exposed to the toxicant. After 28 days of transport, optic nerve proteins were examined using SDS-PAGE, fluorography, and computerized densitometry. In both HD-treated groups, neurofilament transport was accelerated relative to age-matched control animals. In addition, the amount of NFH was decreased relative to other neurofilament subunits. The combination of accelerated transport and a diminished proportion of NFH is similar to the observations of neurofilament axonal transport during growth and development. These observations suggest that this persistent, secondary effect is a reparative response to injury that recapitulates axonal growth and development.
Pyle
S J
SJ
Department of Pathology, Children's Hospital, Boston, Massachusetts.
Amarnath
V
V
Graham
D G
DG
Anthony
D C
DC
D000818:Animals; D001369:Axons / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D006588:Hexanones / Q000097:blood / Q000506:poisoning*; D008297:Male; D008970:Molecular Weight; D009454:Neurofibrils / Q000187:drug effects* / Q000648:ultrastructure; D011758:Pyrroles / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D006588:Hexanones; D011758:Pyrroles; C011269:2,5-hexanedione