Urschel B A, Hulsebosch C E
Department of Biomedical Sciences, McMaster University, Hamilton, Ont., Canada.
Brain Res. 1992 Sep 25;591(2):223-38. doi: 10.1016/0006-8993(92)91702-g.
It is clear that nerve growth factor (NGF) has a role in the central nervous system. In order to begin to determine the possible roles of NGF in the CNS, neonatal rats were given daily subcutaneous injections of antibodies to NGF (ANTI-NGF) beginning at birth for a period of one month. By utilizing the monoclonal antibody, 192-IgG, which recognizes the p75 NGF receptor (NGFR), and standard immunohistochemical techniques we have localized p75 NGFR in variously aged ANTI-NGF-treated animals and compared the anatomic localization and relative density of the p75 NGFR immunoreactive (p75 NGFR-I) regions to same age untreated and preimmune sera-treated littermates. We confirm previously reported localizations of p75 NGFR-I in the rat brain. In addition, we demonstrate that p75 NGFR-I levels of ANTI-NGF-treated rats found in the molecular, the granular and the Purkinje cell layers of the cerebellum, the vestibular nuclei, the spinal tract of V and the cochlear nuclei remain at lower concentrations compared to same-age control animals. We also demonstrate that p75 NGFR-I levels in the basal nucleus approaches background levels after ANTI-NGF treatment. We hypothesize that ANTI-NGF biologically inactivates NGF, which over a period of 30 days results in decreased p75 NGFR-I. These results are consistent with neuronal loss in these regions following ANTI-NGF treatment. Furthermore, the immunological methods used to produce the specific deficits in the present study may have broader implications with respect to usefulness as a method for determining the dependency of CNS neuronal populations for a putative neurotrophic factor and as a method for the development of models of neurodegenerative diseases.
显然，神经生长因子（NGF）在中枢神经系统中发挥着作用。为了开始确定NGF在中枢神经系统中可能的作用，从出生起，对新生大鼠每日进行皮下注射抗NGF抗体（ANTI-NGF），持续一个月。通过使用识别p75 NGF受体（NGFR）的单克隆抗体192-IgG和标准免疫组织化学技术，我们在不同年龄的ANTI-NGF处理动物中定位了p75 NGFR，并将p75 NGFR免疫反应性（p75 NGFR-I）区域的解剖定位和相对密度与同年龄未处理和经免疫前血清处理的同窝仔鼠进行了比较。我们证实了先前报道的大鼠脑中p75 NGFR-I的定位。此外，我们证明，与同年龄对照动物相比，在小脑的分子层、颗粒层和浦肯野细胞层、前庭核、三叉神经脊束和耳蜗核中发现的ANTI-NGF处理大鼠的p75 NGFR-I水平保持在较低浓度。我们还证明，ANTI-NGF处理后，基底核中的p75 NGFR-I水平接近背景水平。我们假设ANTI-NGF在生物学上使NGF失活，在30天的时间里导致p75 NGFR-I减少。这些结果与ANTI-NGF处理后这些区域的神经元丢失一致。此外，本研究中用于产生特定缺陷的免疫方法对于作为确定中枢神经系统神经元群体对假定神经营养因子的依赖性的方法以及作为神经退行性疾病模型开发方法的有用性可能具有更广泛的意义。
