Axonal and nueronal degeneration in relation to balance changes in synthesis, transport and degradation of cytoskeletal proteins.

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Dynamic organization and transport of axonal cytoskeletal proteins were investigated using rat dorsal root ganglion cell and ventral horn motoneuron systems, and the following results were obtained.1. Three subpopulations of axonal cytoskeleton were distinguished by their solubility properties in 1% cold Triton X-100 containing buffer ; stably polymerized, dynamic and depolymerized froms. The last form was thought to be transported form.2. Two subcomponents of slow axonal transport were distinguished by their ratc and composition ; slow component a and b (Sca and Scb respectively). The formerconsisted mainly of stably polymerized form and the latter of dynamic form. The average rate of slow axonal transport slowed down with age.3. Separation into Sca and Scb was seen in young adult rat, e. g. 7weeks of age or older, a few weeks after labelling, but not in young rat, e. g. 4 weeks of age. In older rat than 30 weeks, however, a large peak of stably polymerized form appeared at the initia … More l portion of axon, which scarecely migrated distally. From the accumulated peak of stably polymerized form, a population of dynamic form came out during a next few weeks, which was not reorganized into stably polymerized cytoskletons as in the case of young rat. This resulted in functional denervation of distal axon, probably causing axonal and neuronal degeneration.4. From the results above mentioned, it is suggested that the rate of interconversion among three subpopulations of axonal cytosksleton slows down with age, and especially in the older rat, reorganization from dynamic to stably polymerized forms is severely affected. The dynamic form which fails to reconstitute stably polymerized form may be degraded.5. When axon was injured, it quickly respoded to increase dynamic subpopulation along its whole length for repairing the injury. At the same time the rate of slow axonal transport increased, and the synthesis of tubulin and actin in the neuronal cell body also increased after a while.6. The axonal cytoskeleton is not a rigid structure as ever thought, but rather a dynamic one responding promptly to its environmental conditions. Less