ALTERATION IN NEUROFILAMENT AXONAL-TRANSPORT IN THE SCIATIC-NERVE OF THE DIISOPROPYL PHOSPHOROFLUORIDATE (DFP)-TREATED HEN

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester tha t produces organophosphorus ester-induced delayed neurotoxicity (OPIDN ) in hens 7-14 days after a single s.c. dose of 1.7 mg/kg. In this stu dy, hens were treated with a single dose of DFP (1.7 mg/kg, s.c.) 24 h r after [S-35]methionine injection into the sacrolumbar region of thei r spinal cord, and killed 3, 7, 14, or 27 days post-DFP treatment. The rates of transport of labeled high (NF-H), medium (NF-M), and row (NF -L) molecular weight neurofilaments, and tubulin were faster in DFP-tr eated birds than in controls after 3 days. Subsequently, the rate of t ransport of these proteins started falling, so that the peaks of label ed proteins in control and DFP-treated hens were overlapping after 7 d ays. At 14 days, the peaks of NF-H, NF-M, and NF-L in treated hens wer e distinctly behind the corresponding peaks in control hens. This was again followed by an increase in transport of NF-H and NF-L, but not o f NF-M, so that the labeled NF-H and NF-L showed the same pattern in c ontrol and treated hens after 27 days. The transient decrease in NF-H and NF-L axonal transport rate, and recovery correlated in a temporal manner with the previously reported increase of Ca2+/calmodulin-defend ent protein kinase-mediated phosphorylation of neurofilament proteins and inhibition of calpain activity in the sciatic nerve in OPIDN. Prot einase inhibition has been reported recently to result in enhanced pho sphorylation of neurofilaments in some cells. The present study sugges ts that the enhanced phosphorylation of neurofilaments by DFP-increase d Ca2+/carmodulin-defendent protein kinase activity may be contributin g toward alteration in NF axonal transport and the development of OPID N. (C) 1997 Elsevier Science Inc.