Neurofilament gene expression following beta,beta'-iminodipropionitrile (IDPN) intoxication.
beta,beta'-Iminodipropionitrile (IDPN) is an agent that produces a disorganization of the axonal cytoskeleton with massive accumulation of neurofilaments in the proximal axon. Abnormalities in axonal transport of neurofilament proteins and in their phosphorylation occur in this model. In this study we evaluated the gene expression of neurofilament and other cytoskeletal components at an early, intermediate and late stage of intoxication to determine whether this neuropathy is directly due to or secondarily affects the expression of these components. Specific cytoskeletal mRNA expression was evaluated in the spinal cords of rats treated with IDPN for varying durations using Northern analysis and in situ hybridization. Our results show no qualitative or quantitative alteration in the mRNA expression of the neurofilament triplet, alpha-tubulin, alpha-actin or glial fibrillary acidic protein. We conclude that abnormalities at various stages of cytoskeletal processing such as the early disorganization of the cytoskeleton, the impairment of neurofilament transport, and the long-term redistribution of neurofilaments along the axon are not directly due to, nor do they affect the gene expression of cytoskeletal components in IDPN neuropathy.
Parhad
I M
IM
Department of Pathology, University of Calgary, Alta., Canada.
Swedberg
E A
EA
Hoar
D I
DI
Krekoski
C A
CA
Clark
A W
AW
D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005796:Genes / Q000187:drug effects*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D016900:Neurofilament Proteins; D009570:Nitriles / Q000633:toxicity*; D009693:Nucleic Acid Hybridization; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects*
D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile; D004247:DNA