Lee P, Zhuo H, Helke C J
Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, 20814, Bethesda, MD, USA.
Brain Res Mol Brain Res. 2001 Feb 19;87(1):31-41. doi: 10.1016/s0169-328x(00)00277-1.
Neurotrophins and neurotrophin receptors play an important role in survival and growth of injured peripheral nerves. To study the injury-mediated neurotrophic response in autonomic nerves, we investigated changes in mRNA expression of neurotrophins and their receptors in the transected vagus nerve and nodose ganglion. Studies using in situ hybridization histochemistry showed that axotomy of the cervical vagus nerve resulted in increased expression of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and for TrkA, TrkB, and TrkC receptors in non-neuronal cells at both the proximal and distal segments of the transected cervical vagus nerve. Moreover, NGF protein was increased in the distal end, and NT-3 protein was increased in both the proximal and the distal ends of the transected nerve 3 days after axotomy. No change of p75(NTR) mRNA was detected in the transected vagus nerve. The induction of each neurotrophin and Trk receptor mRNA was apparent within 1 day after the axotomy and was sustained at least 14 days. By 45 days after the axotomy, a time when axonal reconnection with target tissue is made (integrity of the nerve-target connection was confirmed by the retrograde transport of FluoroGold from the stomach to vagal cell bodies), the levels of neurotrophin and Trk mRNAs in the vagus nerve declined to pre-axotomy levels. TrkA, TrkC, and p75(NTR) mRNA-containing vagal sensory neurons in the nodose ganglion were reduced in number after cervical vagotomy. Neurotrophin-mRNA-containing neurons were not found in the nodose ganglia from either intact or vagotomized rats. The axotomy-induced up-regulation of neurotrophins and Trk receptors mainly in the non-neuronal cells at or near the site of transection suggests that neurotrophins are involved in the survival and regeneration process of the vagus nerve after injury.
神经营养因子和神经营养因子受体在受损周围神经的存活和生长中起重要作用。为了研究自主神经中损伤介导的神经营养反应，我们调查了横断迷走神经和结状神经节中神经营养因子及其受体的mRNA表达变化。原位杂交组织化学研究表明，颈迷走神经切断术导致神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3）以及TrkA、TrkB和TrkC受体的mRNA在横断颈迷走神经近端和远端的非神经元细胞中表达增加。此外，轴突切断术后3天，NGF蛋白在远端增加，NT-3蛋白在横断神经的近端和远端均增加。在横断的迷走神经中未检测到p75（NTR）mRNA的变化。每种神经营养因子和Trk受体mRNA的诱导在轴突切断术后1天内明显，并至少持续14天。轴突切断术后45天，即与靶组织建立轴突重新连接时（通过从胃到迷走神经细胞体的FluoroGold逆行运输证实神经-靶连接的完整性），迷走神经中神经营养因子和Trk mRNA的水平降至轴突切断术前水平。颈迷走神经切断术后，结状神经节中含有TrkA、TrkC和p75（NTR）mRNA的迷走感觉神经元数量减少。在完整或迷走神经切断的大鼠的结状神经节中均未发现含有神经营养因子mRNA的神经元。轴突切断诱导的神经营养因子和Trk受体主要在横断部位或其附近的非神经元细胞中的上调表明，神经营养因子参与了迷走神经损伤后的存活和再生过程。
