Eleore Lyndell, Vassias Isabelle, Vidal Pierre-Paul, Triller Antoine, de Waele Catherine
LNRS (CNRS-Paris V), Centre Universitaire des Saints-Pères, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
Eur J Neurosci. 2005 Feb;21(3):669-78. doi: 10.1111/j.1460-9568.2005.03887.x.
In the last decade, numerous studies have investigated molecular changes in excitatory glutamatergic receptors in axotomized motoneurons, but few data are available concerning the modulation of inhibitory amino acid receptors. We report here the effect of axotomy on the expression of glycine receptors, gephyrin, vesicular inhibitory amino acid transporter (VIAAT) and synapsin I in rat facial motor neurons as demonstrated by in situ hybridization and immunohistochemistry. The facial nerve trunk was sectioned unilaterally and rats were killed 1, 3, 8, 30 or 60 days after surgery. We investigated the mechanisms underlying the changes in production of these proteins following axotomy by perfusing the facial nerve with colchicine or tetrodotoxin, and injecting cardiotoxin or botulinum toxin independently and unilaterally into the whisker pads of normal rats. Animals were killed 8 days later and processed for immunohistochemistry. The abundance of GlyR subunits and gephyrin fell sharply in the axotomized facial nucleus. This decrease began 1 day after axotomy and was lowest at 8 days, with protein levels returning to normal by day 60. Abnormal synapsin immunolabelling was also observed between days 8 and 60 after axotomy but we detected no change in VIAAT immunoreactivity. The effect of colchicine was similar to, but weaker than, that of axotomy. In contrast, tetrodotoxin, cardiotoxin and botulinum toxin had no significant effect. Thus, axotomy-induced changes probably resulted from a loss of trophic factor transported from the periphery or a positive injury signal, or both. They did not seem to depend on the disruption of activity.
在过去十年中，众多研究调查了轴突切断的运动神经元中兴奋性谷氨酸能受体的分子变化，但关于抑制性氨基酸受体的调节作用的数据却很少。我们在此报告轴突切断对大鼠面神经运动神经元中甘氨酸受体、gephyrin、囊泡抑制性氨基酸转运体（VIAAT）和突触素I表达的影响，这些结果通过原位杂交和免疫组织化学得以证实。单侧切断面神经干，术后1、3、8、30或60天处死大鼠。我们通过向面神经灌注秋水仙碱或河豚毒素，并单独且单侧地向正常大鼠的须垫注射心脏毒素或肉毒杆菌毒素，来研究轴突切断后这些蛋白质产生变化的潜在机制。8天后处死动物并进行免疫组织化学处理。轴突切断的面神经核中甘氨酸受体亚基和gephyrin的丰度急剧下降。这种下降在轴突切断后1天开始，8天时降至最低，到60天时蛋白质水平恢复正常。在轴突切断后的第8天至60天之间也观察到了异常的突触素免疫标记，但我们未检测到VIAAT免疫反应性的变化。秋水仙碱的作用与轴突切断相似，但较弱。相比之下，河豚毒素、心脏毒素和肉毒杆菌毒素没有显著影响。因此，轴突切断诱导的变化可能是由于从外周转运来的营养因子丧失或正向损伤信号，或两者兼而有之。它们似乎并不取决于活动的中断。
