The kinetics of rapid axonal transport and the phenomenon of transport reversal are the main focus of the proposed experiments. Emphasis is placed on determining whether concentration-dependent changes in transport velocity, as demonstrated in bullfrog sympathetic nerves, also occur in somatic nerves and in mammalian nerves. Initially radiotracer and biochemical techniques will be applied. It is also planned to use state-of-the-art optical microscopy and image-processor instrumentation for studies on transport kinetics. This new methodology is expected to settle questons concerning the means by which rapid transport is accelerated when the local concentration of transported material is raised. For experiments on transport reversal, high-affinity monoclonal antibodies to acetylcholinesterase and dopamine-beta-hydroxylase have been produced or are under development. These immunochemical reagents will be used to define the relative flows of their antigens by rapid anterograde and rapid retrograde transport. The antibodies will also be labeled with fluorescent markers for use in image-processor based experiments that seek to define the sources of retrogradely transported material and the structural stages involved in switching of particles between anterograde and retrograde transport. Overall, the experimental program is intended to provide insights into the basic mechanism of rapid axonal transport and transport-reversal. Both of these phenomena are vital to the maintenance of neuronal function and integrity. Since the latter is known to be especially sensitive to disease and environmental toxins, it can be hoped that the results will make some contribution toward the understanding and eventual treatment of peripheral nerve disease.
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