The aim of this proposal is to study the pathogenesis of the Beta, Beta'-iminodipropionitrile (IDPN) model and some of its applications. In IDPN-treated rats, the transport of neurofilament proteins is severely impaired, while the rates of fast anterograde and retrograde transports are not affected; concurrently, a reorganization of axoplasmic organelles takes place with displacement of neurofilaments towards the periphery and of microtubules, mitochondria and smooth endoplasmic reticulum towards the center of axons. Using the peroxidase-antiperoxidase technique and affinity purified polyclonal antibodies to tubulin, microtubule-associated protein 2 (MAP2) and tau factor, monoclonal antibodies to tubulin, MAP2, actin, myosin, tropomyosin, and possibly tau factor, and an antiserum to the 68,000 dalton subunit of neurofilament the organization of axonal cytoskeleton in rats and embryonal chicken motor neurons in culture will be investigated at the light and electron microscope (EM) level following IDPN administration. As an application of the IDPN model, we will study the axonal distribution of proteins of retrograde transport with quantitative EM autoradiography after covalent labelling with (2,3-3H) N-succinimidyl propionate in control and IDPN rats in order to investigate the role of microtubules and other organelles in retrograde transport as we have already done for the fast anterograde transport. Neurofilamentous accumulations, secondary demyelination and gliosis similar to the ones found in IDPN intoxications are also seen in various human metabolic and degenerative dieases, intoxications, dementias, etc. Retrograde transport is a basic neuronal process involved with the growth, maintenance, regeneration and pathology of neurons (e.g., tetanus, poliomyelitis, diabetic neuropathy, dying-back neuropathy caused by zinc pyridinethione, etc.). With the proposed studies we hope to better understand the various interactions among the components of axonal cytoskeleton and mechanism(s) of axoplasmic tranport, derangement of which might be the key to so many neurological diseases.
| Papasozomenos, S C; Binder, L I (1987) Phosphorylation determines two distinct species of Tau in the central nervous system. Cell Motil Cytoskeleton 8:210-26 |
| Papasozomenos, S C; Binder, L I (1986) Microtubule-associated protein 2 (MAP2) is present in astrocytes of the optic nerve but absent from astrocytes of the optic tract. J Neurosci 6:1748-56 |
| Papasozomenos, S C; Payne, M R (1986) Actin immunoreactivity localizes with segregated microtubules and membraneous organelles and in the subaxolemmal region in the beta,beta'-iminodipropionitrile axon. J Neurosci 6:3483-91 |
