Toxic axonal degeneration occurs independent of neurofilament accumulation.

Abstract

Alteration of neurofilament (NF) proteins is considered a critical component and a causative factor for a number of neuropathologies, especially certain neurotoxicities. Correlative observations have supported this hypothesis; the current study tests this relationship by exposure of neurotoxicants to crayfish, a species lacking NFs. Morphological and immunological tests verified the absence of NFs in crayfish peripheral nerve axons. Tail injections of acrylamide (ACR), 2,5-hexanedione (2,5-HD), or 3,4-dimethyl-2,5-HD (3,4-DMHD) produced ataxia and paralysis. Morphological expression of axonal degeneration in a spatial and temporal pattern of progression comparable to mammalian species possessing NFs was observed. With gamma-diketones, time to onset was slower than observed in mammals but relative potency between neurotoxic analogues was maintained. Non-neurotoxic analogues failed to produce any functional signs of neurotoxicity. These data are consistent with the conclusion that NF accumulations are not cause-effect related to axonal degeneration in these models of neurotoxicity and raise questions as to the relationship between accumulation of NF proteins and axonal degeneration in other neuropathological conditions.

• Authors: D W Sickles, J K Pearson, A Beall, A Testino
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 39 Issue 3 Pg. 347-54 (Oct 15 1994) ISSN: 0360-4012 [Print] United States
• PMID: 7869427 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Acrylamides
• Neurofilament Proteins
• Neurotoxins
• Colchicine

Topics

• Acrylamides (toxicity)
• Animals
• Astacoidea (physiology)
• Axons (drug effects, ultrastructure)
• Blotting, Western
• Colchicine (toxicity)
• Nerve Degeneration (drug effects)
• Nerve Fibers (metabolism, ultrastructure)
• Neurofilament Proteins (drug effects, metabolism)
• Neurotoxins (toxicity)
• Rats
• Rats, Sprague-Dawley
• Sciatic Nerve (drug effects, pathology)