Yu J, Wiley R G, Perez-Polo R J
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-0652, USA.
J Neurosci Res. 1996 Jan 15;43(2):213-23. doi: 10.1002/(SICI)1097-4547(19960115)43:2<213::AID-JNR9>3.0.CO;2-J.
Nerve growth factor (NGF) provides critical trophic support to the cholinergic basal forebrain neurons that express high levels of the low-affinity NGF receptor (p75NGFR) in the adult rat brain. Intraventricular injection of 192 IgG-saporin, made by coupling the monoclonal antibody to p75NGFR 192 IgG to the cytotoxin saporin, selectively destroys the p75NGFR-bearing neurons in the basal forebrain and was used here to examine the effects of selective cholinergic lesions on brain NGF protein levels. We showed that 192 IgG-saporin produced significant long-lasting elevation of NGF protein levels in the hippocampus, cortex, and olfactory bulb, with profound reductions of ChAT activities representing complete cholinergic deafferentations of these areas. NGF level was maintained in the basal forebrain, even though there was almost complete loss of p75NGFR-immunoreactive cells and significant decrease of ChAT activity. In addition, a mild glial response was observed in the basal forebrain, and most of the activated astroglia expressed NGF-like immunoreactivity there. The increases in NGF protein levels in the target areas of the basal forebrain were most likely due to loss of cholinergic basal forebrain neurons and retrograde transport of NGF from these areas. Glial-derived NGF is partially responsible for the maintained level of NGF in the basal forebrain after the loss of cholinergic neurons. The accumulation of NGF protein in the target areas may have some effects on synaptic rearrangement in denervated tissues.
神经生长因子（NGF）为成年大鼠脑中表达高水平低亲和力 NGF 受体（p75NGFR）的胆碱能基底前脑神经元提供关键的营养支持。脑室内注射 192 IgG-皂草素（通过将抗 p75NGFR 的单克隆抗体 192 IgG 与细胞毒素皂草素偶联制成）可选择性地破坏基底前脑中表达 p75NGFR 的神经元，在此用于研究选择性胆碱能损伤对脑 NGF 蛋白水平的影响。我们发现，192 IgG-皂草素使海马、皮层和嗅球中的 NGF 蛋白水平显著且持久升高，同时胆碱乙酰转移酶（ChAT）活性大幅降低，表明这些区域完全失去了胆碱能传入神经。尽管基底前脑中几乎完全丧失了 p75NGFR 免疫反应性细胞且 ChAT 活性显著下降，但 NGF 水平在基底前脑中仍得以维持。此外，在基底前脑中观察到轻度的胶质细胞反应，并且大多数活化的星形胶质细胞在那里表达 NGF 样免疫反应性。基底前脑靶区域中 NGF 蛋白水平的升高很可能是由于胆碱能基底前脑神经元的丧失以及 NGF 从这些区域的逆行运输所致。胶质细胞衍生的 NGF 部分负责胆碱能神经元丧失后基底前脑中 NGF 水平的维持。NGF 蛋白在靶区域的积累可能对去神经组织中的突触重排有一定影响。
