These experiments are intended to provide basic information about the anatomical localization and source of immunoglobins in the normal spinal cord and motor nerves, and the uptake of antineuronal antibodies by motor neurons. They will test certain aspects of the hypothesis that antibodies are taken up from the periphery into nerve terminals and transported retrogradely to become localized in alpha motor neurons as part of a normal physiological process that may be involved in the pathogenesis of certain diseases of the nervous system. We will examine the kinetics of uptake of radiolabelled nonspecific and antineuronal antibodies. Specific antineuronal antibodies from previously studied hybridoma cell lines such as A2B5 (neuron specific cell surface antigen) will be produced and tested for their usefulness in developing an animal model of paraproteinemic axonal neuropathy or neuronopathy as well as in studies of the uptake of antineuronal antibodies. We will also study the uptake of xenogeneic antibodies by the neonatal rat central nervous system. These studies have the potential of providing insight for the pathogenesis of congenital nervous system disease as well as the mechanism of action of anti-nerve growth factor antibodies on the regeneration of neuronal processes in the central nervous system. These studies will provide additional basic information about the relationship between alpha motor neurons of the spinal cord and the humoral immune system and will provide tools and information which should be useful in future studies of the pathogenesis of central and peripheral nervous system disease.
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