Befort Katia, Karchewski Laurie, Lanoue Christopher, Woolf Clifford J
Neural Plasticity Research Group, Department of Anaesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Eur J Neurosci. 2003 Aug;18(4):911-22. doi: 10.1046/j.1460-9568.2003.02827.x.
The growth arrest and DNA damage-inducible gene 45 alpha (Gadd45a) was one of 240 genes found previously by high density oligonucleotide microarray analysis to be regulated in the rat L4 and L5 dorsal root ganglia 3 days after transection of the sciatic nerve (>four-fold up-regulation). The Gadd45a mRNA expression profile investigated by northern blot, RNase protection assay and in situ hybridization in the rat shows negligible constitutive mRNA levels in embryonic, neonatal or adult intact dorsal root ganglia. Within 24 h of a sciatic nerve injury, a very large induction is found that persists for as long as regeneration of injured fibres is prevented by peripheral nerve ligation. When axons are allowed to regrow following sciatic nerve crush injury, Gadd45a expression is terminated at later time points, when levels of other markers of injury return towards normal. Colocalization with activating transcription factor 3-LI and c-jun mRNA implies that all peripherally injured primary sensory and motor neurons express Gadd45a mRNA. Injury to the central axons of dorsal root ganglion neurons produces only a minimal induction of Gadd45a while peripheral inflammation is without effect. Gadd45a is a specific marker of the presence of peripheral axonal injury in adult primary sensory and motor neurons.
生长停滞与DNA损伤诱导基因45α（Gadd45a）是先前通过高密度寡核苷酸微阵列分析在坐骨神经横断3天后的大鼠L4和L5背根神经节中发现的240个被调控基因之一（上调超过四倍）。通过Northern印迹、核糖核酸酶保护分析和原位杂交对大鼠Gadd45a mRNA表达谱进行的研究表明，在胚胎、新生或成年完整背根神经节中，组成型mRNA水平可忽略不计。在坐骨神经损伤后24小时内，可发现非常大的诱导作用，只要通过周围神经结扎阻止受损纤维的再生，这种诱导作用就会持续。当坐骨神经挤压伤后轴突允许再生时，Gadd45a表达在后期时间点终止，此时其他损伤标志物的水平恢复正常。与激活转录因子3-LI和c-jun mRNA共定位意味着所有外周损伤的初级感觉和运动神经元都表达Gadd45a mRNA。背根神经节神经元的中枢轴突损伤仅产生最小程度的Gadd45a诱导，而外周炎症则无影响。Gadd45a是成年初级感觉和运动神经元中外周轴突损伤存在的特异性标志物。
