Toxic axonal degeneration occurs independent of neurofilament accumulation.
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.
Sickles
D W
DW
Department of Cellular Biology and Anatomy, School of Medicine, Medical College of Georgia, Augusta 30912-2000.
Pearson
J K
JK
Beall
A
A
Testino
A
A
D000178:Acrylamides / Q000633:toxicity; D000818:Animals; D003400:Astacoidea / Q000502:physiology*; D001369:Axons / Q000187:drug effects* / Q000648:ultrastructure; D015153:Blotting, Western; D003078:Colchicine / Q000633:toxicity; D009410:Nerve Degeneration / Q000187:drug effects*; D009412:Nerve Fibers / Q000378:metabolism* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology
D000178:Acrylamides; D016900:Neurofilament Proteins; D009498:Neurotoxins; D003078:Colchicine