Molliver D C, Radeke M J, Feinstein S C, Snider W D
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Comp Neurol. 1995 Oct 23;361(3):404-16. doi: 10.1002/cne.903610305.
Investigations into the biological actions of nerve growth factor (NGF) have shown that dorsal root ganglion (DRG) neurons subserving nociception require NGF for survival and maintenance of phenotype. This discovery suggests that the signaling NGF receptor, TrkA, can be used as a marker for nociceptive neurons. In this study, we have used antibodies to TrkA, in conjunction with cell biological markers that show a restricted distribution in the DRG, to further characterize subsets of DRG neurons that are dependent upon NGF. Staining for TrkA labeled small and medium-sized neurons that composed 47% of all neurons in thoracic ganglia. Double-labeling with antibodies to the high molecular weight neurofilament protein (NFH), a marker for neurons with myelinated axons, demonstrated that TrkA staining is found in only a small subset of myelinated neurons. Surprisingly, many DRG neurons were not labeled by either TrkA or NFH. These neurons had small soma areas, contained the intermediate filament protein peripherin, and were labeled by the lectin BSI, identifying them as neurons likely to have unmyelinated axons. In addition, small TrkA-negative neurons were extensively labeled by antibodies to the intermediate filament protein alpha-internexin, the delta isoform of protein kinase C, and by the BSI isolectin BSI-B4. In order to assess the potential functions of TrkA-negative small neurons, we examined their projections to the dorsal horn of the spinal cord. TrkA-immunoreactivity in the spinal cord was restricted to lamina I and the outer region of lamina II (IIo), similar to staining for calcitonin gene-related peptide. In contrast, the central projections of TrkA-negative neurons, as visualized by BSI-B4 staining, were particularly dense in lamina IIi. Our results suggest that TrkA-expressing and non-TrkA-expressing small neurons compose functionally distinct populations of DRG neurons.
对神经生长因子（NGF）生物学作用的研究表明，负责痛觉感受的背根神经节（DRG）神经元需要NGF来维持生存和表型。这一发现表明，信号传导型NGF受体TrkA可作为伤害性神经元的标志物。在本研究中，我们使用抗TrkA抗体，并结合在DRG中呈局限性分布的细胞生物学标志物，以进一步表征依赖NGF的DRG神经元亚群。TrkA染色标记了中小型神经元，这些神经元占胸段神经节中所有神经元的47%。用抗高分子量神经丝蛋白（NFH）抗体进行双重标记，NFH是有髓轴突神经元的标志物，结果显示TrkA染色仅在一小部分有髓神经元中发现。令人惊讶的是，许多DRG神经元未被TrkA或NFH标记。这些神经元胞体面积小，含有中间丝蛋白外周蛋白，并且被凝集素BSI标记，表明它们可能是具有无髓轴突的神经元。此外，小的TrkA阴性神经元被抗中间丝蛋白α-互连蛋白、蛋白激酶C的δ亚型抗体以及BSI异凝集素BSI-B4广泛标记。为了评估TrkA阴性小神经元的潜在功能，我们检查了它们向脊髓背角的投射。脊髓中的TrkA免疫反应性仅限于I层和II层外层（IIo），类似于降钙素基因相关肽的染色。相比之下，通过BSI-B4染色可视化的TrkA阴性神经元的中枢投射在IIi层特别密集。我们的结果表明，表达TrkA和不表达TrkA的小神经元构成了功能上不同的DRG神经元群体。
