Blottner D, Herdegen T
Department of Anatomy, Benjamin Franklin University Clinics, Freie Universität Berlin, Germany.
Neuroscience. 1998 Jan;82(1):283-92. doi: 10.1016/s0306-4522(97)00287-x.
The immediate-early gene encoded transcription factor c-Jun is highly inducible following axotomy and therefore serves as a valuable marker in neuronal de- and regeneration. As the signals that may trigger c-Jun expression are still obscure, molecules derived from lesioned neurons and/or their targets such as growth factors or cytokines have been proposed as candidates for interneuronal transcriptional regulation in vivo. We therefore tested whether local administration of the neuroprotective cytokine fibroblast growth factor type-2 in vivo has an effect on the axotomy-induced nuclear expression patterns of the activator protein-1 transcription factors c-Fos and JunB, or c-Jun in the spinal cord-intermedolateral nucleus-adrenal axis lesion paradigm in the rat. Partial axotomy of preganglionic nerve fibres by selective unilateral removal of the adrenal medulla resulted in strong staining patterns of c-Jun in the nuclei of preganglionic cell bodies located in the spinal intermediolateral cell column identified by in vivo retrograde prelabelling with the fluorescent tracer Fast Blue prior to lesion. Axotomy-induced nuclear c-Jun expression was highly increased when compared with the moderate baseline expression in normal or sham-operated animals. In animals treated with fibroblast growth factor-2 gelfoams implanted to the lesioned adrenal gland the nuclear c-Jun staining pattern is reduced or even absent from these neurons. By contrast, c-Fos and JunB induction did not occur in the intermediolateral nucleus in the lesion paradigm investigated. These results support the idea of functional links between neurotrophic cytokines such as fibroblast growth factor-2 and transcriptional effectors such as c-Jun. The target derived fibroblast growth factor-2 thus may signal the intactness of the neuron-target axis resulting in suppression of central extrinsic neurons and promotion of neuroprotective gene activation. Neuronal survival in absence of c-Jun indicates that c-Jun exerts negative actions in vulnerated neurons.
即早基因编码的转录因子c-Jun在轴突切断后具有高度可诱导性，因此是神经元退变和再生的一个重要标志物。由于触发c-Jun表达的信号仍不清楚，来自受损神经元和/或其靶标的分子，如生长因子或细胞因子，已被认为是体内神经元间转录调控的候选分子。因此，我们测试了在体内局部施用神经保护细胞因子成纤维细胞生长因子2，是否会对大鼠脊髓-中间外侧核-肾上腺轴损伤模型中轴突切断诱导的激活蛋白-1转录因子c-Fos、JunB或c-Jun的核表达模式产生影响。通过选择性单侧切除肾上腺髓质对节前神经纤维进行部分轴突切断，导致位于脊髓中间外侧细胞柱的节前细胞体细胞核中c-Jun出现强染色模式，这是在损伤前用荧光示踪剂快蓝进行体内逆行预标记确定的。与正常或假手术动物的中度基线表达相比，轴突切断诱导的核c-Jun表达显著增加。在用植入受损肾上腺的成纤维细胞生长因子2明胶海绵治疗的动物中，这些神经元的核c-Jun染色模式减少甚至消失。相比之下，在所研究的损伤模型中，中间外侧核未出现c-Fos和JunB的诱导。这些结果支持了神经营养细胞因子如成纤维细胞生长因子2与转录效应因子如c-Jun之间存在功能联系的观点。因此，靶标衍生的成纤维细胞生长因子2可能标志着神经元-靶标轴的完整性，从而导致中枢外在神经元的抑制和神经保护基因激活的促进。缺乏c-Jun时神经元的存活表明c-Jun在受损神经元中发挥负性作用。
