Krekoski C A, Parhad I M, Clark A W
Department of Pathology, University of Calgary, Alberta, Canada.
J Neurosci Res. 1996 Jan 1;43(1):1-11. doi: 10.1002/jnr.490430102.
The actions of nerve growth factor (NGF) are mediated by two receptor proteins, trk and p75. Recent evidence indicates that NGF upregulates the expression of both trk and p75 in responsive neurons including rat dorsal root ganglion (DRG) neurons. Axotomy by disconnecting the neuron from its source of target-derived NGF is predicted to lead to the downregulation of trk and p75 expression. However, previous studies of the effects of axotomy on trk and p75 mRNA expression in rat DRG have yielded discrepant results. We report that following sciatic nerve crush, trk and p75 mRNA levels in L4-L6 DRG decrease to approximately 50% of control levels at 4-14 days, return to control levels by 30 days, and are increased by approximately 30% at 60 days. Similar changes are observed following nerve transection although mRNA levels are slower in returning to normal and do not exceed control levels at later timepoints. Thus, trk and p75 expression decline early following target disconnection and later recover irrespective of target reinnervation. These observations indicate that target derived NGF is required for the maintenance of NGF receptor expression in adult rat DRG neurons and that non-target derived factors can appropriate this function following peripheral nerve injury.
神经生长因子（NGF）的作用由两种受体蛋白介导，即trk和p75。最近的证据表明，NGF上调了包括大鼠背根神经节（DRG）神经元在内的反应性神经元中trk和p75的表达。通过切断神经元与靶源性NGF来源的联系进行轴突切断术预计会导致trk和p75表达下调。然而，先前关于轴突切断术对大鼠DRG中trk和p75 mRNA表达影响的研究结果并不一致。我们报告，坐骨神经挤压后，L4-L6 DRG中的trk和p75 mRNA水平在4-14天时降至对照水平的约50%，30天时恢复到对照水平，60天时增加约30%。神经横断后也观察到类似变化，尽管mRNA水平恢复正常的速度较慢，且在后期时间点未超过对照水平。因此，trk和p75表达在靶标断开连接后早期下降，后期恢复，与靶标重新支配无关。这些观察结果表明，靶源性NGF是成年大鼠DRG神经元中NGF受体表达维持所必需的，并且非靶源性因子在周围神经损伤后可以发挥这一功能。
