Axonal degeneration and axonal caliber alterations following combined beta,beta'-iminodipropionitrile (IDPN) and acrylamide administration.
A new model of neurofilamentous axonal abnormality is described which employs combined administration of beta,beta'-iminodipropionitrile (IDPN) and acrylamide (AC). The model was developed to test the hypothesis that IDPN-induced swelling increases the vulnerability of the distal axon to a second neurotoxic chemical insult. Rats were given a single intraperitoneal (IP) injection of IDPN (1.5 g/kg) one week before receiving a single injection of AC (75 mg/kg, IP). Axonal degeneration was observed at multiple levels along the sciatic nerve at two weeks (with reference to IDPN administration), and was not progressive up to five weeks. Quantitation of degenerating fibers demonstrated that the extent of degeneration increased distally along the sciatic nerve. Single administration of either IDPN or AC did not produce degeneration. Thus, IDPN-induced neurofilamentous swellings alter the susceptibility of the axon to AC neurotoxicity. Two variations of this model were also studied. First, rats given five daily injections of AC (30 mg/kg, IP) beginning one week following IDPN administration developed accumulations of fast axonally transported materials in IDPN-induced microtubule channels. Second, rats given chronic injections of AC (30 mg/kg, IP, five days/week, for four weeks), to reduce the delivery of neurofilaments to the proximal axon, developed less prominent axonal enlargements when challenged with IDPN. Thus, axonal atrophy can mask the development of neurofilamentous axonal swellings.
Gold
B G
BG
Department of Pharmacology and Toxicology, College of Pharmacy, Rutgers University, Piscataway, New Jersey.
Halleck
M M
MM
D020106:Acrylamide; D000178:Acrylamides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000187:drug effects*; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000648:ultrastructure*
D000178:Acrylamides; D009570:Nitriles; D020106:Acrylamide; C008110:3,3'-iminodipropionitrile