Krol Karmen M, Kawaja Michael D
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
J Comp Neurol. 2003 Nov 3;466(1):148-60. doi: 10.1002/cne.10888.
Postganglionic sympathetic neurons, which are exquisitely sensitive to small changes in levels of target-derived nerve growth factor (NGF), express two transmembrane receptors: 1) the trkA receptor mediates neuron survival and neurite outgrowth; and 2) the p75 neurotrophin receptor (p75NTR) enhances neuronal responsiveness of trkA to NGF. Elevating levels of NGF induces several morphological and neurochemical alterations in sympathetic neurons, including axonal sprouting, increased levels of p75NTR mRNA relative to trkA mRNA, and increased accumulations of NGF in hypertrophied somata. Spontaneously hypertensive rats (SHR) display both elevated NGF levels and increased sympathetic axonal innervation of the mesenteric vasculature. In this investigation we assessed whether sympathetic neurons innervating the mesenteric vasculature of SHR display other features indicative of increased levels of target-derived NGF. In 5-week-old SHR, levels of both p75NTR and trkA mRNA in mesenteric sympathetic neurons were significantly elevated compared to levels in age-matched control rats. By 15 and 30 weeks of age, levels of p75NTR mRNA expression in mesenteric sympathetic neurons were similar between SHR and control rats. Accumulations of NGF were depleted in the sympathetic somata of 15- and 30-week-old SHR compared to age-matched control rats. Moreover, sympathetic neurons in SHR were not hypertrophied, as the sizes of somata were comparable between SHR and control rats. Our data illustrate that despite having augmented levels of NGF in the mesenteric vasculature, SHR do not display many of the morphological and neurochemical features that are associated with an enhanced responsiveness by sympathetic neurons to elevated levels of target-derived NGF.
节后交感神经元对靶源性神经生长因子（NGF）水平的微小变化极为敏感，表达两种跨膜受体：1）trkA受体介导神经元存活和神经突生长；2）p75神经营养因子受体（p75NTR）增强trkA对NGF的神经元反应性。NGF水平升高会诱导交感神经元发生多种形态和神经化学改变，包括轴突发芽、相对于trkA mRNA而言p75NTR mRNA水平升高，以及肥大的胞体中NGF积累增加。自发性高血压大鼠（SHR）表现出NGF水平升高以及肠系膜血管的交感神经轴突支配增加。在本研究中，我们评估了支配SHR肠系膜血管的交感神经元是否表现出其他表明靶源性NGF水平升高的特征。在5周龄的SHR中，肠系膜交感神经元中p75NTR和trkA mRNA的水平相较于年龄匹配的对照大鼠显著升高。到15周龄和30周龄时，SHR和对照大鼠肠系膜交感神经元中p75NTR mRNA的表达水平相似。与年龄匹配的对照大鼠相比，15周龄和30周龄SHR的交感神经元胞体中NGF积累减少。此外，SHR中的交感神经元没有肥大，因为SHR和对照大鼠的胞体大小相当。我们的数据表明，尽管SHR肠系膜血管中的NGF水平升高，但它们并未表现出许多与交感神经元对升高的靶源性NGF水平反应增强相关的形态和神经化学特征。
