Stephens Heather E, Belliveau Anne C, Gupta Jagdish S, Mirkovic Slobodan, Kablar Boris
Dalhousie University, Department of Anatomy and Neurobiology, 5850 College Street, Halifax, NS, Canada B3H 5X1.
Int J Dev Neurosci. 2005 Nov;23(7):613-20. doi: 10.1016/j.ijdevneu.2005.07.002. Epub 2005 Sep 22.
The aim of this study was to approach the question of neuronal dependence on neurotrophins during embryonic development in mice in a way other than gene targeting. We employed amyogenic mouse embryos and fetuses that develop without any skeletal myoblasts or skeletal muscle and consequently lose motor and proprioceptive neurons. We hypothesized that if, in spite of the complete inability to maintain motor and proprioceptive neurons, the remaining spinal and dorsal root ganglia tissues of amyogenic fetuses still contain any of the neurotrophins, that particular neurotrophin alone is not sufficient for the maintenance of motor and proprioceptive neurons. Moreover, if the remaining spinal and dorsal root ganglia tissues still contain any of the neurotrophins, that particular neurotrophin alone may be sufficient for the maintenance of the remaining neurons (i.e., mostly non-muscle- and a few muscle-innervating neurons). To test the role of the spinal cord and dorsal root ganglia tissues in the maintenance of its neurons, we performed immunohistochemistry employing double-mutant and control tissues and antibodies against neurotrophins and their receptors. Our data suggested that: (a) during the peak of motor neuron cell death, the spinal cord and dorsal root ganglia distribution of neurotrophins was not altered; (b) the distribution of BDNF, NT-4/5, TrkB and TrkC, and not NT-3, was necessary for the maintenance of the spinal cord motor neurons; (c) the distribution of BDNF, NT-4/5 and TrkC, and not NT-3 and Trk B, was necessary for the maintenance of the DRG proprioceptive neurons; (d) NT-3 was responsible for the maintenance of the remaining neurons and glia in the spinal cord and dorsal root ganglia (possibly via TrkB).
本研究的目的是以基因靶向以外的方式探讨小鼠胚胎发育过程中神经元对神经营养因子的依赖性问题。我们使用了无肌生成的小鼠胚胎和胎儿，它们在发育过程中没有任何骨骼肌成肌细胞或骨骼肌，因此会失去运动和本体感觉神经元。我们假设，尽管完全无法维持运动和本体感觉神经元，但无肌生成胎儿剩余的脊髓和背根神经节组织中若仍含有任何神经营养因子，那么仅该特定神经营养因子不足以维持运动和本体感觉神经元。此外，如果剩余的脊髓和背根神经节组织仍含有任何神经营养因子，那么仅该特定神经营养因子可能足以维持剩余的神经元（即主要是非肌肉支配和少数肌肉支配的神经元）。为了测试脊髓和背根神经节组织在维持其神经元中的作用，我们使用双突变和对照组织以及针对神经营养因子及其受体的抗体进行了免疫组织化学实验。我们的数据表明：(a) 在运动神经元细胞死亡高峰期，神经营养因子在脊髓和背根神经节中的分布没有改变；(b) 脑源性神经营养因子（BDNF）、神经营养因子-4/5（NT-4/5）、酪氨酸激酶受体B（TrkB）和酪氨酸激酶受体C（TrkC）的分布对维持脊髓运动神经元是必要的，而神经营养因子-3（NT-3）不是；(c) BDNF、NT-4/5和TrkC的分布对维持背根神经节本体感觉神经元是必要的，而NT-3和TrkB不是；(d) NT-3负责维持脊髓和背根神经节中剩余的神经元和神经胶质细胞（可能通过TrkB）。
