Apostolova Galina, Dorn Roland, Ka Sojeong, Hallböök Finn, Lundeberg Joakim, Liser Keren, Hakim Vicky, Brodski Claude, Michaelidis Theologos M, Dechant Georg
Institute for Neuroscience, Innsbruck Medical University, MZA, Anichstrasse 35, 6020 Innsbruck, Austria.
Mol Cell Neurosci. 2007 Jul;35(3):397-408. doi: 10.1016/j.mcn.2007.03.014. Epub 2007 Apr 1.
During late developmental phases individual sympathetic neurons undergo a switch from noradrenergic to cholinergic neurotransmission. This phenomenon of plasticity depends on target-derived signals in vivo and is triggered by neurotrophic factors in neuronal cultures. To analyze genome-wide expression differences between the two transmitter phenotypes we employed DNA microarrays. RNA expression profiles were obtained from chick paravertebral sympathetic ganglia, treated with neurotrophin 3, glial cell line-derived neurotrophic factor or ciliary neurotrophic factor, all of which stimulate cholinergic differentiation. Results were compared with the effect of nerve growth factor, which functions as a pro-noradrenergic stimulus. The gene set common to all three comparisons defined the noradrenergic and cholinergic synexpression groups. Several functional categories, such as signal transduction, G-protein-coupled signaling, cation transport, neurogenesis and synaptic transmission, were enriched in these groups. Experiments based on the prediction that some of the identified genes play a role in the neurotransmitter switch identified bone morphogenetic protein signaling as an inhibitor of cholinergic differentiation.
在发育后期，单个交感神经元会经历从去甲肾上腺素能神经传递到胆碱能神经传递的转变。这种可塑性现象在体内依赖于靶源信号，并由神经元培养中的神经营养因子触发。为了分析两种递质表型之间全基因组的表达差异，我们采用了DNA微阵列技术。从鸡的椎旁交感神经节获取RNA表达谱，用神经生长因子3、胶质细胞系源性神经营养因子或睫状神经营养因子处理，所有这些因子都能刺激胆碱能分化。将结果与神经生长因子的作用进行比较，神经生长因子起促去甲肾上腺素能刺激作用。所有三个比较共有的基因集定义了去甲肾上腺素能和胆碱能共表达组。这些组中富集了几个功能类别，如信号转导、G蛋白偶联信号传导、阳离子转运、神经发生和突触传递。基于一些已鉴定基因在神经递质转换中起作用的预测进行的实验，确定骨形态发生蛋白信号传导是胆碱能分化的抑制剂。
