Loy R, Lachyankar M B, Condon P J, Poluha D K, Ross A H
Department of Neurology, University of Rochester School of Medicine and Dentistry, New York 14620.
Exp Neurol. 1994 Dec;130(2):377-86. doi: 10.1006/exnr.1994.1217.
Long-term physiological responses of nerve growth factor (NGF) and other neurotrophins require gene regulation and likely depend on retrograde axonal transport of NGF or a signaling molecule activated by ligand-receptor interaction. The low-affinity neurotrophin receptor p75LANR is retrogradely transported, but this receptor is not sufficient for NGF-dependent cell survival or differentiation. In this study we examined the distribution and transport of the TrkA NGF receptor using two anti-peptide polyclonal antibodies and a monoclonal antibody, all of which are TrkA specific. We find that (1) in the adult rat brain TrkA-like immunoreactivity is similar with all antibodies in striatal and basal forebrain neurons, (2) TrkA is upregulated in neuronal and nonneuronal cells near the sites of injury, and (3) TrkA immunoreactivity builds up within the proximal and distal segments of transected fimbrial axons, which is consistent with its transport in the anterograde and retrograde directions. Thus, TrkA may itself be, or be a component of, the neurotrophic intraaxonal messenger by which NGF regulates gene expression in sensitive neurons.
神经生长因子（NGF）和其他神经营养因子的长期生理反应需要基因调控，并且可能依赖于NGF或由配体-受体相互作用激活的信号分子的逆行轴突运输。低亲和力神经营养因子受体p75LANR可逆行运输，但该受体不足以介导依赖NGF的细胞存活或分化。在本研究中，我们使用三种均对TrkA具有特异性的抗体（两种抗肽多克隆抗体和一种单克隆抗体）研究了TrkA NGF受体的分布和运输。我们发现：（1）在成年大鼠脑中，纹状体和基底前脑神经元中，所有抗体检测到的TrkA样免疫反应性相似；（2）在损伤部位附近的神经元和非神经元细胞中，TrkA表达上调；（3）在横断的海马伞轴突的近端和远端节段中，TrkA免疫反应性增强，这与其顺行和逆行运输一致。因此，TrkA本身可能是，或者是神经营养性轴突内信使的一个组成部分，通过它NGF可调节敏感神经元中的基因表达。
