Tuszynski M H, U H S, Amaral D G, Gage F H
Department of Neurosciences, University of California, La Jolla 92093.
J Neurosci. 1990 Nov;10(11):3604-14. doi: 10.1523/JNEUROSCI.10-11-03604.1990.
NGF is a protein that promotes survival, differentiation, and process extension of selected neuronal populations during development and, in some cases, in the mature organism. Previous lesion and aging studies in the rat have shown that intracerebroventricular NGF infusions can prevent degenerative changes in basal forebrain cholinergic neurons. We sought to determine whether salutory effects of NGF occur in the primate brain. Cholinergic fibers of the septohippocampal projection in the primate were surgically transected, followed by infusion of either a vehicle or an NGF solution into the ventricular system for a 4-week period. Quantification of cholinergic neurons in the medial septal nucleus at the end of the infusion period demonstrated that only 45 +/- 5% of cholinergic neurons could be identified after fornix lesions in vehicle-infused animals, whereas 80 +/- 6% of neurons were visible in NGF-treated animals. Thus, NGF substantially reduced lesion-induced cholinergic neuronal degeneration in the adult primate brain. This finding may be relevant to the hypothesis that NGF has potential use as a cholinergic "neurotrophic-factor therapy," given that loss of basal forebrain cholinergic neurons is common in Alzheimer's disease.
神经生长因子（NGF）是一种蛋白质，在发育过程中，以及在某些情况下在成熟生物体中，可促进特定神经元群体的存活、分化和轴突生长。先前对大鼠进行的损伤和衰老研究表明，脑室内注入NGF可预防基底前脑胆碱能神经元的退行性变化。我们试图确定NGF在灵长类动物大脑中是否也有有益作用。通过手术切断灵长类动物海马隔区投射的胆碱能纤维，随后在4周内将载体或NGF溶液注入脑室系统。注入期结束时，对内侧隔核中的胆碱能神经元进行定量分析，结果显示，在注入载体的动物中，穹窿损伤后仅45±5%的胆碱能神经元可被识别，而在接受NGF治疗的动物中，80±6%的神经元可见。因此，NGF可显著减少成年灵长类动物大脑中损伤诱导的胆碱能神经元变性。鉴于基底前脑胆碱能神经元的丧失在阿尔茨海默病中很常见，这一发现可能与NGF有潜力用作胆碱能“神经营养因子疗法”的假说相关。
