Pilot--Central Synaptic Function in Diabetic Rat

Morehouse College, Atlanta GA

Investigators

Linked publications & trials

Abstract

In diabetic polyneuropathy large diameter sensory and motor axons innervating the lower limb and hands[unreadable] demonstrate dysfunctional responses that result in positive (gain of function) and negative (loss of function)[unreadable] symptoms. These functional changes are assumed to be caused by morphological alterations in peripheral[unreadable] nerve including axonal degeneration, demyelination, and ultimately neuronal death, yet may initially be[unreadable] independent of such changes. The goal of this project is to explain the loss of sensorimotor function in[unreadable] locomotor pathways of diabetics. Specifically, data will determine whether there is an early and preceding[unreadable] loss of function at central sensorimotor synapses caused by a decline in trophic support. Data will help[unreadable] determine the early changes in motoneuron and proprioceptor function and synaptic efficacy in diabetes.[unreadable] Loss of sensorimotor function in diabetic patients show that movement disorders may be due to functional[unreadable] losses in proprioceptors synapsing on the motor neurons subserving the behavior, in the motoneurons[unreadable] themselves, or in the processing of information at the synapse between primary afferents and motoneurons.[unreadable] Loss of trophic support may aid in producing the neuropathy experienced by many diabetics. In adult rats[unreadable] made diabetic, direct intra-axonal or intrasomatic records of neuronal function will be made followed by[unreadable] morphological study of those neurons. Data will show the extent of damage, if any, that occurs at early time[unreadable] points following induction of disease, whether dysfunction is due to central or peripheral changes in structure[unreadable] or function, and whether neurons in the peripheral or central nervous system can be rescued by direct local[unreadable] delivery of low doses of insulin or its associated growth factors, IGF-I or -II.[unreadable] Of the approximately 18 million people in the United States that are diabetic, 12% will have neuropathy, and[unreadable] after 25 years of disease 50% will have it. Although many treatments have been attempted, no therapy has[unreadable] completely reversed neuropathy. The results will help to elaborate on the neurons involved in locomotor[unreadable] dysfunction in diabetes, and aid in directing effective therapeutic regimens using novel drug delivery systems[unreadable] with an appropriate time course when treatment is likely to be more effective.