Axonal neurofilaments are nonessential elements of toxicant-induced reductions in fast axonal transport: video-enhanced differential interference microscopy in peripheral nervous system axons.
Neurofilament modification and accumulation, occurring in toxicant-induced neuropathies, has been proposed to compromise fast axonal transport and contribute to neurological symptoms or pathology. The current study compares the effects of the neurotoxicants acrylamide (ACR) and 2,5-hexanedione (2,5-HD) on the quantity of fast, bidirectional vesicular traffic within isolated mouse sciatic nerve axons from transgenic mice lacking axonal neurofilaments (Eyer and Peterson, Neuron 12, 1-20, 1994) and nontransgenic littermates possessing neurofilaments. Fast anterograde and retrograde membrane bound organelle (MBO) traffic was quantitated within axons, before and after toxicant exposure, using video-enhanced differential interference contrast (AVEC-DIC) microscopy. Addition of 0.7 mM ACR to the buffer bathing the nerve produced a time-dependent reduction in bidirectional transport with a similar time to onset and magnitude in both transgenic and nontransgenic mice. 2,5-HD (4 mM) exposure reduced bidirectional vesicle traffic by a similar amount in both transgenic and nontransgenic animals. The time to onset of the transport reduction was less and the magnitude of the reduction was greater with 2,5-HD compared to ACR. A single 10-min exposure to ACR or 2,5-HD produced a similar reduction in transport to that produced by prolonged (1 h) exposure. Nonneurotoxic propionamide or 3,4-hexanedione (3,4-HD) produced no changes in bidirectional transport in either transgenic or nontransgenic animals. We conclude that ACR or 2,5-HD produces a rapid, saturable, nonreversible, neurotoxicant-specific reduction in fast bidirectional transport within isolated peripheral nerve axons. These actions are mediated through direct modification of axonal component(s), which are independent of toxicant-induced modifications of, or accumulations of, neurofilaments.
Stone
J D
JD
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia, 30912, USA.
Peterson
A P
AP
Eyer
J
J
Oblak
T G
TG
Sickles
D W
DW
D020106:Acrylamide / Q000633:toxicity; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000577:Amides / Q000633:toxicity; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006588:Hexanones / Q000633:toxicity; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008857:Microscopy, Interference; D018715:Microscopy, Video; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D015388:Organelles / Q000187:drug effects / Q000378:metabolism; D017933:Peripheral Nervous System / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D000577:Amides; D006588:Hexanones; D009498:Neurotoxins; D020106:Acrylamide; C011269:2,5-hexanedione; C034666:propionamide