Effect of IGF-I and neurotrophin-3 on gracile neuroaxonal dystrophy in diabetic and aging rats.
Effect of IGF-I and neurotrophin-3 on gracile neuroaxonal dystrophy in diabetic and aging rats.
复制标题
IGF-I 和神经营养蛋白-3 对糖尿病和衰老大鼠纤细神经轴突营养不良的影响。
DOI：
10.1016/s0006-8993(00)02602-0
复制
发表时间：
2000
期刊：
影响因子：
2.9
通讯作者：
Ohara,S
中科院分区：
文献类型：
--
作者：
Schmidt,RE;Dorsey,DA;Beaudet,LN;Plurad,SB;Parvin,CA;Ohara,S
神经轴突营养不良（Neuroaxonal dystrophy， NAD）是一种独特的轴突病，其特征是由于各种亚细胞细胞器的积累而导致轴突和神经末梢急剧肿胀，发生在老年动物和人类的感觉神经元向髓细核的中央突起中，并在许多疾病和实验条件下发生。虽然其发病机制尚不清楚，但可能的机制包括轴突再生、侧枝发芽和突触可塑性异常，这可能反映了神经营养支持的改变。在目前的研究中，我们已经定量地证明了衰老导致预期的纤细NAD频率显著增加；然而，大量营养不良的轴突在6到10个月之间发育，比预期的要早。虽然有报道称糖尿病会增加遗传性糖尿病BB大鼠细束感觉神经元中枢过程中NAD的频率，但我们发现，与年龄匹配的对照组相比，8-10个月的链脲佐菌素诱导的糖尿病导致细束核中营养不良的轴突减少。神经营养因子-3 （NT-3）和胰岛素样生长因子- i （IGF-I）已被证明会影响突触可塑性（与NAD的发病机制有关），在牺牲前的最后两个月给予神经营养因子-3和胰岛素样生长因子- i并没有影响对照组或糖尿病患者纤薄型NAD的发生频率。在纤细核的感觉终端提供了一个简单的，表征良好的实验系统，其中神经轴突营养不良的发病机制和预防问题可以解决。
Neuroaxonal dystrophy (NAD), a distinctive axonopathy characterized by dramatic swelling of preterminal axons and nerve terminals by the accumulation of a variety of subcellular organelles, develops in the central projections of sensory neurons to medullary gracile nuclei in aged animals and man, and in a number of diseases and experimental conditions. Although its pathogenesis is unknown, proposed mechanisms include abnormalities of axonal regeneration, collateral sprouting and synaptic plasticity which may reflect alteration in neurotrophic support. In the current study, we have demonstrated quantitatively that aging causes the expected marked increase in the frequency of gracile NAD; however, substantial numbers of dystrophic axons develop between 6 and 10 months of age, earlier than expected. Although diabetes has been reported to increase the frequency of NAD in the central processes of sensory neurons in the gracile fasciculus of genetically diabetic BB rats, we have found that 8–10 months of streptozotocin-induced diabetes results in fewer dystrophic axons in the gracile nucleus than in age-matched controls. Administration of neurotrophin-3 (NT-3) and insulin-like growth factor-I (IGF-I), which have been shown to affect synaptic plasticity (implicated in the pathogenesis of NAD), for the last two months before sacrifice did not affect the frequency of gracile NAD in controls or diabetics. The sensory terminals in the gracile nuclei provide a simple, well-characterized experimental system in which questions of pathogenesis and prevention of neuroaxonal dystrophy can be addressed.