title: Neurofilaments are non-essential elements of toxicant-induced reductions in fast axonal transport: pulse labeling in CNS neurons.
abstract: Acrylamide (ACR) and g-diketones (g-DK) produce distal sensory-motor neuropathy in a variety of species, including humans. The specific molecular site and mechanism of toxicant action leading to specific morphological and behavioral abnormalities requires definition. The relative roles of fast anterograde axonal transport and neurofilaments (NF) are investigated using optic nerves of mice, with and without axonal neurofilaments. Segmental analysis, following pulse labeling with 3H-leucine into the vitreous body, was used to detect changes in fast anterograde transport in the optic nerve and tract. Single injections of ACR significantly reduced the quantity of radiolabeled proteins transported in both transgenic (lacking NF) and non-transgenic (containing NF) mice by 68.4% and 46.2%, respectively. Similarly, single injections of 2,5-hexanedione (2,5-HD) reduced the quantity of radiolabeled transport in transgenic and non-transgenic mice by 55.2% and 47.1%, respectively. Equimolar doses of propionamide and 3,4-hexanedione (non-neurotoxic analogues of ACR and 2,5-HD, respectively) produced no changes in the quantity or apparent rate of optic nerve transport. Additionally, no differences in quantity or apparent rate of transport between transgenic and non-transgenic animals were observed under control or experimental conditions. Therefore, ACR and 2,5-HD reduce the quantity of fast anterograde axonal transport in mouse CNS axons in a comparable amount to previously reported reductions in rat PNS axons. The absence of axonal neurofilaments had no effect on normal fast transport. Furthermore, the presence or absence of neurofilaments did not alter the effect of these toxicants on fast axonal transport. We conclude that toxicant-induced reductions in fast axonal transport are unrelated to ACR and g-diketone effects on NF or their accumulation.
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Stone
authors.forename: A P
authors.initials: AP
authors.lastname: Peterson
authors.forename: J
authors.initials: J
authors.lastname: Eyer
authors.forename: D W
authors.initials: DW
authors.lastname: Sickles
mesh_terms: D020106:Acrylamide / Q000633:toxicity; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D006588:Hexanones / Q000633:toxicity; D007700:Kinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity
chemical_list: D006588:Hexanones; D016900:Neurofilament Proteins; D009498:Neurotoxins; D020106:Acrylamide; C011269:2,5-hexanedione