Pilot--Central Synaptic Function in Diabetic Rat

糖尿病多发性神经病变中支配肢体和手部的大直径感觉神经和运动神经轴突 表现出导致积极(功能获得)和消极(功能丧失)的功能障碍反应 症状。这些功能改变被认为是由外周的形态改变引起的 神经包括轴突变性，脱髓鞘，最终神经元死亡，但最初可能是 不受这些变化的影响。这个项目的目的是为了解释人类感觉运动功能的丧失 糖尿病患者的运动通路。具体地说，数据将决定是否存在先期和先期 中枢感觉运动性突触功能的丧失是由于营养支持的减少引起的。数据将有所帮助 确定糖尿病患者运动神经元和本体感受器功能及突触效能的早期变化。 糖尿病患者感觉运动功能的丧失表明运动障碍可能是由于功能性 为行为服务的运动神经元上本体感受器突触的损失，在运动神经元 或者在初级传入神经元和运动神经元之间的突触的信息处理中。 营养支持的丧失可能有助于许多糖尿病患者所经历的神经病变的产生。在成年大鼠中 糖尿病患者，直接记录轴突内或椎体内的神经功能 对这些神经元进行了形态研究。数据将显示早期发生的损坏程度(如果有的话 诱发疾病后的穴位，无论功能障碍是由于中枢还是外周结构的变化 或功能，以及周围或中枢神经系统中的神经元是否可以通过直接局部挽救 注射低剂量胰岛素或与其相关的生长因子IGF-I或IGF-II。 在美国大约1800万糖尿病患者中，12%会有神经病变， 在患病25年后，50%的人会患上这种病。虽然已经尝试了许多治疗方法，但还没有一种治疗方法 完全逆转了神经病。这一结果将有助于详细说明参与运动的神经元。 糖尿病的功能障碍，并帮助指导使用新的药物输送系统的有效治疗方案 有一个适当的疗程，当治疗可能更有效时。

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