Carroll S L, Silos-Santiago I, Frese S E, Ruit K G, Milbrandt J, Snider W D
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Neuron. 1992 Oct;9(4):779-88. doi: 10.1016/0896-6273(92)90040-k.
In utero immune deprivation of the neurotrophic molecule nerve growth factor (NGF) results in the death of most, but not all, mammalian dorsal root ganglion (DRG) neurons. The recent identification of trk, trkB, and trkC as the putative high affinity receptors for NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively, has allowed an examination of whether their expression by DRG neurons correlates with differential sensitivity to immune deprivation of NGF. In situ hybridization demonstrates that virtually all neurons expressing trk are lost during in utero NGF deprivation. Most, if not all, neurons expressing trkB and trkC survive this treatment. In contrast, the low affinity NGF receptor, p75NGFR, is expressed in both NGF deprivation-resistant and -sensitive neurons. These experiments show that DRG neurons expressing trk require NGF for survival. Furthermore, at least some of the DRG neurons that do not require NGF express the high affinity receptor for another neurotrophin. Finally, these experiments provide evidence that trk, and not p75NGFR, is the primary effector of NGF action in vivo.
子宫内对神经营养分子神经生长因子(NGF)进行免疫剥夺会导致大多数(但并非全部)哺乳动物背根神经节(DRG)神经元死亡。最近已确定trk、trkB和trkC分别为NGF、脑源性神经营养因子和神经营养素-3的假定高亲和力受体,这使得人们能够研究DRG神经元对它们的表达是否与对NGF免疫剥夺的不同敏感性相关。原位杂交显示,在子宫内NGF剥夺期间,几乎所有表达trk的神经元都会死亡。大多数(如果不是全部的话)表达trkB和trkC的神经元在这种处理后存活下来。相反,低亲和力NGF受体p75NGFR在对NGF剥夺有抗性和敏感的神经元中均有表达。这些实验表明,表达trk的DRG神经元需要NGF来维持生存。此外,至少一些不需要NGF的DRG神经元表达另一种神经营养素的高亲和力受体。最后,这些实验提供了证据,证明trk而非p75NGFR是体内NGF作用的主要效应分子。