TOXIC AXONAL DEGENERATION OCCURS INDEPENDENT OF NEUROFILAMENT ACCUMULATION

Alteration of neurofilament (NF) proteins is considered a critical com ponent and a causative factor for a number of neuropathologies, especi ally 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 a nd immunological tests verified the absence of NFs in crayfish periphe ral 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 paraly sis. Morphological expression of axonal degeneration in a spatial and temporal pattern of progression comparable to mammalian species posses sing NFs was observed. With gamma-diketones, time to onset was slower than observed in mammals but relative potency between neurotoxic analo gues was maintained. Non-neurotoxic analogues failed to produce any fu nctional signs of neurotoxicity. These data are consistent with the co nclusion that NF accumulations are not cause-effect related to axonal degeneration in these models of neurotoxicity and raise questions as t o the relationship between accumulation of NF proteins and axonal dege neration in other neuropathological conditions. (C) 1994 Wiley-Liss, I nc.