Changes of Cytoskeletal System in Neurodegenerative Disease: Immunohistochemical Characterization of Neurofibrillary Changes Induced by Mitotic Spindle Inhibitors

In experimental neurogenerative diseases, aluminum(Al) intoxication and axotomized sensory neurons showed an abnormal accumulation of neurofilaments(NF) in the neuronal perikarya. These NF contain phosphorylated(ph) epitopes that are not detectable in normal perikaryal NF. Antimitotic drugs also cause accumulations of NF probably by depolymerization of microtubules(MT). The present study was designed to examine immunohistochemical changes of NFs following administration of antimitotic drugs, which result in accumulation of NFs in the cell body through a different pathogenetic mechanism than aluminum. Adult rabbits were injected intracisternally with 25-50µg of maytansine and maytanprine, two antimitotic agents. Tissues were obtained from experimental and control animals and processed for histological and immunocytochemical examinations. Large bundles of NF in the perikarya and proximal processes of large neurons from experimental animals reacted intensely with monoclonal antibodies(mAb) to ph epitopes of 200 KDa NF subunit as well as with mAb recognizing nonphosphorylated(non-ph) NF epitopes. Neuronal perikarya from control animals immunoreacted only with mAb to non-ph NF Immunoreaction of Ab to the microtubule associated protein 2(MAP-2) and to tubulin was similar in neurons from experimental and control animals. No immunoreaction was detected with antibodies to tau proteins. The abnormal presence of ph epitopes in accumulating NF under different conditions indicate that neurons affected in different diseases show aberrant phosphorylation of NF proteins associated with functional impairment.