Impairment of cytoskeletal protein transport due to aging or beta,beta'-iminodipropionitrile intoxication in the rat sciatic nerve.

Three major age-related changes in cytoskeletal organization and metabolism in the axon were observed by comparing slow axonal transport in the sciatic nerves of rats aged 7-80 weeks: (a) a progressive decrease in the rate of slow axonal transport, (b) a tight association of cold-insoluble tubulin with the neurofilament (NF) proteins and (c) an accelerated proteolysis of the severely retarded proteins, especially NF proteins. These changes were reproduced to a large extent in the young animal by intoxication with beta,beta'-iminodipropionitrile (IDPN). As IDPN is known to impair the axonal transport of NF proteins and cause segregation of NFs from microtubules, the results indicate that NF-microtubule interaction is one of the major factors regulating the axonal cytoskeleton. The importance of the balance between transport rate and degradation rate in the maintenance of the normal axonal cytoskeleton is stressed especially in the aged animal.