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Abstract:
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Diabetic neuropathy (DN) is a common complication of both diabetes mellitus type I and II. DN has traditionally been described as a “dying-back” neuropathy, where the distal ends of sensory axons degenerate and denervate peripheral tissues. Patients with DN can show a loss of large- and/or small-diameter sensory fibers. When large fibers are involved, the patients exhibit proprioceptive deficits and impaired balance. Muscle spindles are innervated by both sensory and motor neurons and send proprioceptive information about the muscle to the central nervous system. To date, no studies have specifically addressed the innervation of muscle spindles in the setting of DN. We hypothesize that diabetes-induced denervation of muscle spindles underlies, in part, the development of proprioceptive abnormalities in DN. To test this hypothesis, we utilize a mouse model of type I diabetes induced by streptozotocin. To explore the relationship between muscle spindle deficits and proprioception, we are evaluating the proprioceptive abilities of control and diabetic mice using a rotorod, which tests coordination and balance. In addition, muscle spindle innervation is evaluated in the gastrocnemius muscle using immunohistochemical techniques. Using antibodies against S46 to visualize spindle bag fibers and neurofilament heavy chain to visualize sensory and motor axons innervating the spindles, and bungarotoxin to label the neuromuscular junction, the sensory (Ia and II) and motor (gamma) innervation of the spindle is assessed. Overall, these results will provide important information about the relationship between muscle spindles and proprioceptive deficits in DN. |
