Mason M R J, Lieberman A R, Anderson P N
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Eur J Neurosci. 2003 Aug;18(4):789-802. doi: 10.1046/j.1460-9568.2003.02809.x.
The failure of some CNS neurons to up-regulate growth-associated genes following axotomy may contribute to their failure to regenerate axons. We have studied gene expression in rat corticospinal neurons following either proximal (intracortical) or distal (spinal) axotomy. Corticospinal neurons were retrogradely labelled with cholera toxin subunit B prior to intracortical lesions or concomitantly with spinal lesions. Alternate sections of forebrain were immunoreacted for cholera toxin subunit B or processed for mRNA in situ hybridization for ATF3, c-jun, GAP-43, CAP-23, SCG10, L1, CHL1 or krox-24, each of which has been associated with axotomy or axon regeneration in other neurons. Seven days after intracortical axotomy, ATF3, c-jun, GAP-43, SCG10, L1 and CHL1, but not CAP-23 or krox-24, were up-regulated by layer V pyramidal neurons, including identified corticospinal neurons. The maximum distance between the lesion and the neuronal cell bodies that up-regulated genes varied between 300 and 500 microm. However, distal axotomy failed to elicit changes in gene expression in corticospinal neurons. No change in expression of any molecule was seen in the neocortex 1 or 7 days after corticospinal axotomy in the cervical spinal cord. The expression of GAP-43, CAP-23, L1, CHL1 and SCG10 was confirmed to be unaltered after this type of injury in identified retrogradely labelled corticospinal neurons. Thus, while corticospinal neuronal cell bodies fail to respond to spinal axotomy, these cells behave like regeneration-competent neurons, up-regulating a wide range of growth-associated molecules if axotomized within the cerebral cortex.
一些中枢神经系统神经元在轴突切断后未能上调生长相关基因，这可能导致它们无法再生轴突。我们研究了大鼠皮质脊髓神经元在近端（皮质内）或远端（脊髓）轴突切断后的基因表达情况。在进行皮质内损伤之前，或在进行脊髓损伤的同时，用霍乱毒素B亚基对皮质脊髓神经元进行逆行标记。对前脑的交替切片进行霍乱毒素B亚基免疫反应，或进行原位杂交以检测ATF3、c-jun、GAP-43、CAP-23、SCG10、L1、CHL1或krox-24的mRNA，这些基因在其他神经元中均与轴突切断或轴突再生有关。皮质内轴突切断7天后，包括已确定的皮质脊髓神经元在内的V层锥体神经元上调了ATF3、c-jun、GAP-43、SCG10、L1和CHL1，但未上调CAP-23或krox-24。上调基因的损伤部位与神经元细胞体之间的最大距离在300至500微米之间。然而，远端轴突切断未能引起皮质脊髓神经元基因表达的变化。在颈脊髓进行皮质脊髓轴突切断后1天或7天，新皮质中任何分子的表达均未发生变化。在已确定的逆行标记的皮质脊髓神经元中，证实这种类型的损伤后GAP-43、CAP-23、L1、CHL1和SCG10的表达未改变。因此，虽然皮质脊髓神经元细胞体对脊髓轴突切断无反应，但如果在大脑皮质内进行轴突切断，这些细胞表现得像具有再生能力的神经元，会上调多种生长相关分子。
