Seiler Stefanie, Pollini Dario, Di Santo Stefano, Widmer Hans R
aDepartment of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster bGraduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Neuroreport. 2013 Dec 18;24(18):1047-52. doi: 10.1097/WNR.0000000000000063.
The myelin-associated protein Nogo-A and its receptor Nogo-receptor 1 (NgR1) are known as potent growth inhibitors of the adult central nervous system (CNS). Nogo-A is mostly expressed on the surface of oligodendrocytes, but is also found in neurons of the adult and developing CNS. This observation suggests that Nogo-A serves additional functions in the brain. Hence, in the present study, we investigated the effects of antagonizing NgR1 on cultured organotypic and dissociated dopaminergic neurons. For that purpose ventral mesencephalic cultures from E14 rat embryos were grown in absence or presence of the NgR1 antagonist NEP1-40 for 1 week. Treatment with NEP1-40 significantly increased cell densities of tyrosine hydroxylase-immunoreactive neurons. Moreover, organotypic ventral mesencephalic cultures displayed a significantly bigger volume after NEP1-40 treatment. Morphological analysis of tyrosine hydroxylase-positive neurons disclosed longer neurites and higher numbers of primary neurites in dissociated cultures incubated with NEP1-40, whereas soma size was not changed. In conclusion, our findings demonstrate that interfering with Nogo-A signaling by antagonizing NgR1 modulates dopaminergic neuron properties during development. These observations highlight novel aspects of the role of Nogo-A in the CNS and might have an impact in the context of Parkinson's disease.
髓鞘相关蛋白Nogo-A及其受体Nogo受体1（NgR1）是已知的成年中枢神经系统（CNS）的强效生长抑制剂。Nogo-A主要表达于少突胶质细胞表面，但在成年和发育中的CNS的神经元中也有发现。这一观察结果表明Nogo-A在大脑中发挥着额外的功能。因此，在本研究中，我们研究了拮抗NgR1对培养的器官型和分离的多巴胺能神经元的影响。为此，将来自E14大鼠胚胎的腹侧中脑培养物在不存在或存在NgR1拮抗剂NEP1-40的情况下培养1周。用NEP1-40处理显著增加了酪氨酸羟化酶免疫反应性神经元的细胞密度。此外，NEP1-40处理后，器官型腹侧中脑培养物的体积显著增大。对酪氨酸羟化酶阳性神经元的形态学分析显示，在与NEP1-40孵育的分离培养物中，神经突更长，初级神经突数量更多，而胞体大小没有变化。总之，我们的研究结果表明，通过拮抗NgR1干扰Nogo-A信号传导可调节发育过程中多巴胺能神经元的特性。这些观察结果突出了Nogo-A在CNS中的作用的新方面，并且可能对帕金森病的情况产生影响。
