Immunohistochemical study of phosphorylated neurofilaments during the evolution of organophosphorus ester-induced delayed neuropathy (OPIDN).
Organophosphorus ester-induced delayed neuropathy (OPIDN) is manifest by delayed degeneration of distal levels of long myelinated fibers following an appropriate neurotoxic exposure. We investigated the dynamics of cytoskeletal changes during nerve fiber degeneration in this condition, focusing on the immunohistochemistry of axonal phosphorylated neurofilaments. OPIDN was produced in 5-month-old White Leghorn hens using a single 2.5 mg/kg intramuscular dose of phenyl saligenin phosphate. Hens were sacrificed on days 4, 7, 9, 15, and 20, and the tibial nerve branch to the gastrocnemius muscle was studied by light microscopy and immunohistochemistry (using the SMI 31 monoclonal primary antibody to phosphorylated neurofilaments). At post-dosing days 9, 15, and 20 various stages of OPIDN lesions were noted, including axonal swelling and myelinated nerve fiber degeneration. These were associated with intra-axonal cytoskeletal lysis, manifest by loss of immunolabeled phosphorylated neurofilaments, a process consistent with proteolysis. Aggregations of excess axonal phosphorylated neurofilaments were not observed.
Jortner
B S
BS
Laboratory for Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg 24061-0442, USA. bjortner@vt.edu
Perkins
S K
SK
Ehrich
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002645:Chickens; D005260:Female; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D008853:Microscopy; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010766:Phosphorylation; D013979:Tibial Nerve / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007306:Insecticides; D016900:Neurofilament Proteins; D009943:Organophosphorus Compounds; C046357:phenylsaligenin cyclic phosphate