Colby Geoffrey P, Coon Alexander L, Connolly E Sander, Ambron Richard T
Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, Black Building Room 1204, 630 West 168th Street, New York, NY 10032, USA.
Exp Neurol. 2005 Jul;194(1):57-65. doi: 10.1016/j.expneurol.2005.01.024.
Nerve transection induces complex changes in gene regulation and expression that can have profound phenotypic effects on the fate of axotomized neurons. The transcription factors c-Jun and ATF-2 (activating transcription factor-2) are components of a regulatory network that mediates survival, regeneration, and apoptosis following axotomy in rodents. The activation and function of c-Jun and ATF-2 after nerve injury have not been examined in primates. Using a novel model of cranial nerve injury in baboons, we have examined the temporality of c-Jun activation (phosphorylation) in cranial nerve (CN) III and CN VI neurons and ATF-2 activation in CN VI neurons at 2, 4, and 9 days post-injury by immunohistochemistry. Furthermore, we have addressed whether the activation of these factors is associated with apoptosis by the TUNEL assay. We report that activated c-Jun is present in CN III and CN VI neurons ipsilateral to axotomy at 2, 4, and 9 days post-injury, but not in neurons contralateral to injury. Additionally, CN VI neurons ipsilateral to injury at 4 and 9 days contain activated ATF-2. Furthermore, no evidence of TUNEL reactivity was observed in either nucleus, regardless of laterality, at any of the examined time points. These findings suggest that activation of both c-Jun and ATF-2 does not mediate apoptosis in axotomized primate CN III and CN VI neurons at time points up to 9 days. This report serves as a basic inquiry into the neuronal response to cranial nerve injury in primates.
神经切断会引发基因调控和表达的复杂变化，这些变化可能对轴突切断的神经元命运产生深远的表型影响。转录因子c-Jun和激活转录因子2（ATF-2）是一个调节网络的组成部分，该网络介导啮齿动物轴突切断后的存活、再生和凋亡。神经损伤后c-Jun和ATF-2的激活及功能尚未在灵长类动物中进行研究。我们使用一种新型的狒狒颅神经损伤模型，通过免疫组织化学检测了损伤后2天、4天和9天动眼神经（CN）III和外展神经（CN）VI神经元中c-Jun的激活（磷酸化）以及CN VI神经元中ATF-2的激活情况。此外，我们通过TUNEL检测探讨了这些因子的激活是否与凋亡相关。我们报告称，损伤后2天、4天和9天，激活的c-Jun存在于轴突切断同侧的CN III和CN VI神经元中，但不存在于损伤对侧的神经元中。此外，损伤同侧的CN VI神经元在4天和9天时含有激活的ATF-2。此外，在任何检测时间点，无论哪一侧，两个核中均未观察到TUNEL反应性的证据。这些发现表明，在长达9天的时间点内，c-Jun和ATF-2的激活均未介导灵长类动物轴突切断的CN III和CN VI神经元的凋亡。本报告是对灵长类动物颅神经损伤神经元反应的一项基础研究。
