Streptozotocin-induced diabetes reduces retrograde axonal transport in the afferent and efferent vagus nerve.
Streptozotocin-induced diabetes reduces retrograde axonal transport in the afferent and efferent vagus nerve.
复制标题
链脲佐菌素诱导的糖尿病减少传入和传出迷走神经的逆行轴突运输。
DOI：
10.1016/s0006-8993(02)02645-8
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发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Helke,CindaJ
中科院分区：
文献类型：
--
作者：
Lee,PaekGyu;Cai,Fang;Helke,CindaJ
糖尿病引起的神经功能改变包括神经营养因子的逆行轴突运输减少。先前显示，在链脲佐菌素（STZ）诱导的糖尿病大鼠迷走神经中内源性神经生长因子（NGF）和神经营养因子-3（NT-3）的轴突积聚减少。在本研究中，在糖尿病16或24周后，胃或心房（两个迷走神经支配的器官）中的NGF和NT-3蛋白或mRNA水平没有变化。此外，糖尿病大鼠迷走神经和迷走传入结状神经节中神经营养素受体（p75，TrkA，TrkC）mRNA的量没有减少。这些数据表明，无论是减少获得目标源性神经营养因子，也没有相关的神经营养因子受体的损失占糖尿病引起的神经营养因子的逆行轴突运输的改变。为了评估糖尿病是否会导致轴突运输的缺陷，这可能不是特定的神经营养素运输，我们研究了神经元示踪剂（FluoroGold，FG）的能力，逆行运输的迷走神经元的控制和糖尿病大鼠。在迷走神经靶组织（胃）注射FG后，分别在结状神经节和迷走神经背侧运动核中计数FG标记的迷走神经传入和传出神经元的数量。糖尿病24周后，FG逆行运输到STZ糖尿病大鼠的传入和传出迷走神经元比对照组少50%以上。糖尿病引起的FG逆行轴突运输缺陷可能反映了传入和传出迷走神经中基本轴突运输机制的改变，这有助于先前观察到的神经营养因子运输减少。
Diabetes-induced alterations in nerve function include reductions in the retrograde axonal transport of neurotrophins. A decreased axonal accumulation of endogenous nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the vagus nerve of streptozotocin (STZ)-induced diabetic rats was previously shown. In the current study, no changes in the NGF and NT-3 protein or mRNA levels in the stomach or atrium, two vagally innervated organs, were noted after 16 or 24 weeks of diabetes. Moreover, the amounts of neurotrophin receptor (p75, TrkA, TrkC) mRNAs in the vagus nerve and vagal afferent nodose ganglion were not reduced in diabetic rats. These data suggest that neither diminished access to target-derived neurotrophins nor the loss of relevant neurotrophin receptors accounts for the diabetes-induced alteration in the retrograde axonal transport of neurotrophins. To assess whether diabetes causes a defect in axonal transport that may not be specific to neurotrophin transport, we studied the ability of a neuronal tracer (FluoroGold, FG) to be retrogradely transported by vagal neurons of control and diabetic rats. After vagal target tissue (stomach) injections of FG, the numbers of FG-labeled afferent and efferent vagal neurons were counted in the nodose ganglion and in the dorsal motor nucleus of the vagus, respectively. After 24 weeks of diabetes, FG was retrogradely transported to more than 50% fewer afferent and efferent vagal neurons in the STZ-diabetic compared to control rats. The diabetes-induced deficit in retrograde axonal transport of FG is likely to reflect alterations in basic axonal transport mechanisms in both the afferent and efferent vagus nerve that contribute to the previously observed reductions in neurotrophin transport.