Navascues J, Casafont I, Villagra N T, Lafarga M, Berciano M T
Department of Anatomy and Cell Biology and Biomedicine Unit Associated with C.S.I.C., University of Cantabria, Santander, Spain.
J Neurocytol. 2004 Jul;33(4):393-405. doi: 10.1023/B:NEUR.0000046570.90442.43.
In this study we have taken advantage of the high nuclear responsiveness of type A sensory ganglia neurons to variations of cellular activity to investigate the reorganization and dynamics of nuclear compartments involved in transcription and RNA processing in response to neuronal injury. As experimental model we have used the inflammatory injury of the peripheral nerve endings induced by formalin injection in the areas of ophthalmic/maxillary nerve distribution. We have performed immunofluorescence and confocal laser microscopy analysis with specific antibodies for different nuclear compartments and ultrastructural analysis. The initial response to neuronal injury, within the 3 days post-injury, consisted of chromatin condensation, reduction in the expression level of acetylated histone H4, accumulation of perichromatin granules, reorganization of splicing factors in prominent nuclear speckles, reduction in the number of Cajal bodies and nucleolar alterations. These changes tended to revert by day 7 post-injury and are consistent with a transient inhibition of transcription and RNA processing. Moreover, we have observed an early and sustained expression of the transcription factor c-Jun. These results illustrate the transcription-dependent organization of nuclear compartments in type A trigeminal neurons and also support the importance of the nuclear response to axonal injury as a key component in the regenerative capacity of this neuronal population.
在本研究中,我们利用 A 型感觉神经节神经元对细胞活动变化的高核反应性,来研究参与转录和 RNA 加工的核区室在神经元损伤时的重组和动态变化。作为实验模型,我们采用了在眼神经/上颌神经分布区域注射福尔马林诱导外周神经末梢发生炎性损伤的方法。我们使用针对不同核区室的特异性抗体进行了免疫荧光和共聚焦激光显微镜分析以及超微结构分析。神经元损伤后的最初反应,在损伤后 3 天内,包括染色质浓缩、乙酰化组蛋白 H4 表达水平降低、染色质周边颗粒积累、剪接因子在显著的核斑中重新组织、卡哈尔体数量减少以及核仁改变。这些变化在损伤后第 7 天趋于恢复,这与转录和 RNA 加工的短暂抑制一致。此外,我们观察到转录因子 c-Jun 的早期持续表达。这些结果说明了 A 型三叉神经元中核区室的转录依赖性组织,也支持了核对轴突损伤的反应作为该神经元群体再生能力关键组成部分的重要性。