Carbon disulfide axonopathy. Another experimental model characterized by acceleration of neurofilament transport and distinct changes of axonal size

The role of axonal transport in the development of structural changes of axons can be examined using experimental models. Two different compounds, 2,5-hexanedione (2,5-HD) and carbon disulfide (CS₂), cause axonopathies characterized by the formation of neurofilaments (NF) containing enlargements in preterminal regions of central and peripheral axons. These axonopathies are excellent experimental models of the giant axonal neuropathies, a group of acquired and inherited human diseases of the central and peripheral nervous system. We previously reported that following administration of 2,5-HD, transport of NF is accelerated while number of NF and cross-sectional area are decreased in regions of the axon proximal to the enlargements. We proposed that acceleration of NF transport leads to a 'longitudinal' redistribution of NF which are decreased proximally and increased distally where they form the NF containing axonal enlargements. We have now carried out morphometric, transport and immunocytohemical studies in primart visual axons of rats exposed to CS₂. NF-containing axonal enlargements were observed in optic tract and superior colliculus and they increased in number in a proximodistal direction. There was no detectable axonal degeneration and the cross-sectional area of axons proximal to the enlargements was decreased. Transport of NF was markedly accelerated. Immunostaining showed that all 3 NF subunits and phosphorylated epitopes of the 200-kDa NF subunit were present in the NF-containing axonal enlargements. All these findings were similar to those previously observed in the 2,5-HD axonopathy. It is suggested that acceleration of NF transport and proximal reduction of axon caliber are the hallmarks of giant axonal neuropathies with distal NF-containing enlargements at stages of the disease preceding axonal degeneration. The type of transport alteration produced by CS₂ and 2,5-HD is best explained by a direct effect of these compounds on the axonal cytoskeleton. The findings that 2,5-HD and CS₂, which have different chemical properties, produce almost identical changes in slow transport indicates that despite their chemical difference, these two compounds alter the axonal cytoskeleton in a similar way.