CHARACTERIZATION & TREATMENT OF LARGE SENSORY FIBER PERIPHERAL NEUROPATHY IN DIABETIC MICE

Abstract

Patients with large-fiber diabetic sensorimotor polyneuropathy (DPN) can develop altered sensorimotor function. Gait and balance control are regulated, in part, through large sensory nerves innervating muscle spindles. The overall goal was to characterize DPN in an animal model of diabetes and explore the hypothesis that the symptoms could be due to aberrant spindle innervation. We evaluated sensorimotor behavior in diabetic mice and used immunohistochemistry to quantify the Ia axon innervation of spindles. Diabetic mice displayed altered balance and were found to have variations in the morphology of Ia axons compared to very consistent spindle innervation in nondiabetics. Treatment with insulin successfully reversed sensorimotor deficits and decreased diabetes-driven spindle Ia innervation variability. Low-intensity aerobic exercise therapy also repaired sensorimotor deficits in diabetic mice, but had no effect on muscle spindle Ia axon innervation morphology. This work provides insight into large-fiber DPN, and will hopefully lead to future treatment strategies in humans.