Axonal transport of neurofilament is accelerated in peripheral nerve during 2,5-hexanedione intoxication.
The neurotoxic compound 2,5-hexanedione (2,5-HD) causes an axonopathy characterized by the presence of neurofilament (NF)-containing enlargements in the preterminal segments of central and peripheral axons. The 2,5-HD axonopathy is a good model for human acquired and inherited giant axonal neuropathies. Recently, we reported that following 2,5-HD administration, axonal transport of NF is markedly and selectively accelerated in the primary visual system. We have now studied slow axonal transport in the sciatic system of rats intoxicated with 0.5% 2,5-HD in drinking water. Following radiolabeling, transported proteins were examined after polyacrylamide gel electrophoresis and fluorography. The bulk of radiolabeled NF subunits was located 30-50 mm from the spinal cord in 2,5-HD treated animals and 10-25 mm in controls. The rate of transport of the three NF subunits was 0.7 mm/day in controls and 1.2 mm/day in 2,5-HD treated animals. The rate of transport of tubulin was not significantly changed. Electrophysiological studies of soleus nerve and muscle showed no evidence of denervation after 6 weeks of intoxication. It is concluded that, following 2,5-HD administration, transport of NF is preferentially accelerated in both central and peripheral axons. A pathogenetic mechanism based on the acceleration of NF transport is proposed, which may explain the formation and the distal or proximal location of NF-containing axonal enlargements in giant axonopathies.
Monaco
S
S
Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106.
Jacob
J
J
Jenich
H
H
Patton
A
A
Autilio-Gambetti
L
L
Gambetti
P
P
D000200:Action Potentials; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D005260:Female; D006588:Hexanones / Q000633:toxicity*; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007659:Ketones / Q000633:toxicity*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D006588:Hexanones; D007381:Intermediate Filament Proteins; D007659:Ketones; D016900:Neurofilament Proteins; D009498:Neurotoxins; C011269:2,5-hexanedione