NEUROTROPHINS AND VISCERAL AFFERENT NEURONS IN DIABETES

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Diabetic autonomic neuropathy alters autonomic reflexes and is associated with morbidity and a poor prognosis for diabetic patients. A component of this dysfunction is due to altered visceral afferent neurons. Injury to visceral afferent neurons of the vagus and glossopharyngeal nerves disrupts important cardiovascular, respiratory and gastrointestinal reflexes. The objectives for this project are to better characterize diabetes induced alterations in visceral afferent neurons, and to study the actions of the neurotrophin family of neurotrophic factors in visceral afferent nerve function/dysfunction in diabetes. The investigators will test the hypotheses that diabetes induces metabolic, neurochemical, neuropathologic, microvascular and functional alterations in visceral afferent neurons that can be alleviated with appropriate neurotrophic support. They will use streptozotocin treated diabetic rats (with/without insulin replacement) to characterize diabetes induced alterations in visceral afferent nerves and their ganglia at various times after initiation of experimental diabetes. To determine whether an impairment of neurotrophin actions may be involved in diabetes induced alterations in visceral afferent neurons, they will assess whether the delivery of neurotrophins to visceral afferent neurons is affected by altered retrograde external transport and/or by altered levels of neurotrophins in diabetes, and the effect of diabetes on the presence of neurotrophin receptors. Finally, the ability of specific neurotrophins to alleviate diabetes induced alterations and to affect visceral afferent neurons in diabetes will be determined.