Description): Over the course of a lifetime, a significant percentage of the population needs medical attention for some form of neuropathy, such as low back pain, diabetic neuropathy or carpal tunnel syndrome. Due to their prevalence and complexity of treatment, neuropathies have a major financial impact in health care. Compromise of axonal transport may contribute to the pathophysiology of several clinical neuropathies. The goal of the candidate's proposed research is to understand the role of axonal transport in peripheral nerve function. Axons are dependent on continuous replenishment of membrane proteins and on the feedback provided by materials taken up at nerve terminals. The length of the nerve dictates that bi-directional transport be tightly regulated. Interruption of axonal transport leads to Wallerian degeneration of axons distal to the site of impairment. Therefore, several neuropathies are thought to have impaired axonal transport. However, there have been few controlled investigations of the functional consequences of impaired axonal transport or of the aspects of transport that may contribute to peripheral neuropathy. The proposed specific aims address these two issues, and seek to identify physical interventions that may alter function in neuropathic nerves.
The first aim i s to determine how the function of peripheral nerves is impaired by disruption of axonal transport. To accomplish this aim, peripher-al nerves in which axonal transport has been experimentally impaired will be tested for their ability to respond to sensory stimuli, using behavioral tests and electrophysiological techniques.
The second aim i s to determine what aspects of axonal transport are disrupted in peripheral neuropathies. To address this aim, peripheral poly- or mononeuropathy will be experimentally induced, and anterograde or retrograde axonal transport will be tested for impairment, using biochemical and morphological techniques. Additional observations will be made of the components required for axonal transport, specifically, energy stores, divalent cations and cytoskeletal structural framework.
The third aim i s to identify physical interventions that improve or impair axonal transport and nerve function in peripheral neuropathies. To accomplish this aim, neuropathic nerves with demonstrated alterations in axonal transport will be further exposed to nerve compression, extremity mobilization or immobilization. Nerve function will be assessed using behavioral tests and electrophysiological techniques.
| Topp, K S; Tanner, K D; Levine, J D (2000) Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat. J Comp Neurol 424:563-76 |
