Abnormal muscle spindle innervation and large-fiber neuropathy in diabetic mice
Abnormal muscle spindle innervation and large-fiber neuropathy in diabetic mice
复制标题
DOI：
10.2337/db08-0022
复制
发表时间：
2008-06-01
期刊：
影响因子：
7.7
通讯作者：
Wright, Douglas E.
中科院分区：
文献类型：
--
作者：
Muller, Karra A.;Ryals, Janelle M.;Wright, Douglas E.
目的：大纤维糖尿病多发神经病变（DPN）导致平衡和步态异常，使患者有跌倒的风险。支配肌肉纺锤体的大感觉轴突为平衡和步态提供反馈，当受损时，可引起感觉运动功能的改变。本研究旨在确定1型和2型糖尿病小鼠模型中大纤维DPN的症状是否与肌梭神经支配的改变有关。此外，用胰岛素治疗糖尿病小鼠，以评估感觉运动和纺锤体缺陷是否可逆。研究设计和方法：对注射链脲佐菌素（STZ）未治疗和治疗的C57BU6小鼠进行行为评估，以量化糖尿病引起的平衡和步态缺陷。采用免疫组织化学和共聚焦显微镜对注射stz的C57BU6和db/db小鼠进行纺锤体Ia轴突神经支配的定量分析。结果：注射stz的C57BL/6小鼠表现出明显的进行性感觉运动功能障碍。对糖尿病C57BL/6梭状体的la神经支配模式的分析显示了一系列提示la轴突变性和/或再生的异常。多种异常的la纤维形态导致轴突宽度和旋间距离（IRD）的显著变化。同样，与db（+）小鼠相比，db/db小鼠的ird表现出显著的变异性，这表明1型和2型糖尿病模型中都发生了轴突损伤。与非糖尿病小鼠相比，胰岛素治疗改善了行为缺陷并恢复了la纤维神经支配。结论：与小纤维类似，轴突易患糖尿病，其损伤可能导致平衡和步态障碍。此外，这些研究提供了一种新的方法来检测糖尿病引起的大纤维功能障碍的治疗干预措施。
OBJECTIVE-Large-fiber diabetic polyneuropathy (DPN) leads to balance and gait abnormalities, placing patients at risk for falls. Large sensory axons innervating muscle spindles provide feedback for balance and gait and, when damaged, can cause altered sensorimotor function. This study aimed to determine whether symptoms of large-fiber DPN in type 1 and type 2 diabetic mouse models are related to alterations in muscle spindle innervation. In addition, diabetic mice were treated with insulin to assess whether sensorimotor and spindle deficits were reversible.RESEARCH DESIGN AND METHODS-Behavioral assessments were performed in untreated and treated streptozotocin (STZ)-injected C57BU6 mice to quantitate diabetes-induced deficits in balance and gait. Quantification of Ia axon innervation of spindles was carried out using immunohistochemistry and confocal microscopy on STZ-injected C57BU6 and db/db mice.RESULTS-STZ-injected C57BL/6 mice displayed significant and progressive sensorimotor dysfunction. Analysis of la innervation patterns of diabetic C57BL/6 spindles revealed a range of abnormalities suggestive of la axon degeneration and/or regeneration. The multiple abnormal la fiber morphologies resulted in substantial variability in axonal width and inter-rotational distance (IRD). Likewise, db/db mice displayed significant variability in their IRDs compared with db(+) mice, suggesting that damage to la axons occurs in both type 1 and type 2 diabetes models. Insulin treatment improved behavioral deficits and restored la fiber innervation in comparison with nondiabetic mice.CONCLUSIONS-Similar to small fibers, la axons are vulnerable to diabetes, and their damage may contribute to balance and gait deficits. In addition, these studies provide a novel method to assay therapeutic interventions designed for diabetes-induced large-fiber dysfunction.