Junard E O, Montero C N, Hefti F
Andrus Gerontology Center, University of Southern California, Los Angeles 90089.
Exp Neurol. 1990 Oct;110(1):25-38. doi: 10.1016/0014-4886(90)90048-w.
Nerve growth factor (NGF), a neurotrophic factor acting on cholinergic neurons of the basal forebrain, has been proposed as a treatment for Alzheimer's disease. Experimental support for its pharmacological use is derived from short-term studies showing that intraventricular administration of NGF during 2-4 weeks protects cholinergic cell bodies from lesion-induced degeneration, stimulates synthesis of choline acetyltransferase, and improves various behavioral impairments. To investigate the consequences of long-term NGF administration, we tested whether cholinergic cell bodies are protected from lesion-induced degeneration and whether cholinergic axons are stimulated to regrow into the denervated hippocampus following fimbrial transections. We found that intraventricular injections of NGF twice a week for 5 months to adult rats resulted in extended protection of cholinergic cell bodies from lesion-induced degeneration and did not produce obvious detrimental effects on the animals. NGF treatment mildly stimulated growth of cholinergic neurites within the 2-mm area directly adjacent to the fimbrial lesion but it failed to induce significant homotypic growth of cholinergic neurites into the deafferented hippocampus.
神经生长因子（NGF）是一种作用于基底前脑胆碱能神经元的神经营养因子，已被提议用于治疗阿尔茨海默病。其药理学应用的实验依据来自短期研究，这些研究表明，在2至4周内脑室内给予NGF可保护胆碱能细胞体免受损伤诱导的退变，刺激胆碱乙酰转移酶的合成，并改善各种行为障碍。为了研究长期给予NGF的后果，我们测试了胆碱能细胞体是否能免受损伤诱导的退变，以及在海马伞横断后胆碱能轴突是否会被刺激重新生长到去神经支配的海马中。我们发现，成年大鼠每周两次脑室内注射NGF，持续5个月，可延长胆碱能细胞体免受损伤诱导退变的保护时间，且对动物未产生明显的有害影响。NGF治疗轻度刺激了与海马伞损伤直接相邻的2毫米区域内胆碱能神经突的生长，但未能诱导胆碱能神经突向去传入海马的显著同型生长。
