Fernyhough P, Diemel L T, Tomlinson D R
Department of Pharmacology, St. Bartholomew's and Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, UK.
Diabetologia. 1998 Mar;41(3):300-6. doi: 10.1007/s001250050907.
Neurotrophin-3 (NT-3) acts as a target-derived neurotrophic factor for large calibre sensory neurones and plays a role in the maintenance of the adult phenotype of proprioceptive and mechanoreceptive fibres. Large fibre sensory neuropathy is common in diabetes mellitus and the aim of this study was to determine whether endogenous NT-3-dependent neurotrophic support was sub-optimal in the streptozotocin-diabetic rat. NT-3 gene expression was analysed by Northern blotting and ELISA in hindlimb skeletal muscle and found to be decreased by up to 70% (p < 0.05) in rats with 4-6 weeks of diabetes compared to aged-matched controls. Treatment of other diabetic rats with insulin prevented development of deficits of both NT-3 protein and of its mRNA. The deficits in target tissue production of NT-3 were coincident with significant decreases in its anterograde and retrograde axonal transport in sciatic nerve at 6 weeks of diabetes. The mRNA expression in lumbar dorsal root ganglia of the specific receptor for NT-3, trkC, was also down-regulated at 12 weeks of diabetes by 50% (p < 0.05). The observed decreases in NT-3 target tissue production and related axonal transport suggest that large calibre sensory neurones expressing trkC may be receiving sub-optimal neurotrophic support in experimental diabetes.
神经营养因子-3（NT-3）作为大口径感觉神经元的靶源性神经营养因子，在本体感觉和机械感受性纤维的成年表型维持中发挥作用。大纤维感觉神经病变在糖尿病中很常见，本研究的目的是确定在链脲佐菌素诱导的糖尿病大鼠中，内源性NT-3依赖性神经营养支持是否不足。通过Northern印迹法和酶联免疫吸附测定法分析后肢骨骼肌中的NT-3基因表达，发现与年龄匹配的对照组相比，糖尿病4-6周的大鼠中NT-3基因表达降低了70%（p<0.05）。用胰岛素治疗其他糖尿病大鼠可防止NT-3蛋白及其mRNA的缺乏。糖尿病6周时，NT-3靶组织产生的缺乏与坐骨神经中其顺行和逆行轴突运输的显著减少同时出现。糖尿病12周时，NT-3特异性受体trkC在腰背根神经节中的mRNA表达也下调了50%（p<0.05）。观察到的NT-3靶组织产生和相关轴突运输的减少表明，在实验性糖尿病中，表达trkC的大口径感觉神经元可能接受了不足的神经营养支持。
