Lapchak P A, Araujo D M, Hefti F
Department of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los Angeles.
Neuroscience. 1994 May;60(2):293-8. doi: 10.1016/0306-4522(94)90243-7.
Recent studies with nerve growth factor (NGF) have identified the pharmacological actions of this neurotrophin in a variety of animal models that mimic some of the neurotransmitter deficits that occur in Alzheimer's disease (AD, for reviews see Refs 7, 15, 17, 19). Based upon extensive pharmacological studies, NGF has been characterized as a crucial maintenance factor for adult cholinergic neurons of the septo-hippocampal and basalo-cortical pathways. Among the reported actions of NGF is an attenuation of lesion-induced decrements in presynaptic and postsynaptic cholinergic markers and functions in the hippocampal formation. Thus, in studies that used partial fimbriectomies to parallel the cholinergic neurodegeneration that occurs in AD, intraventricularly administered nerve growth factor prevented the loss of choline acetyltransferase (ChAT) and acetylcholinesterase immunoreactivity in the septum and increased a variety of presynaptic cholinergic markers involved in the synthesis, storage and release of the neurotransmitter acetylcholine (for reviews see Refs 7, 17, 19). More specifically, chronic NGF treatment attenuates lesion-induced reductions in hippocampal ChAT activity and high-affinity choline uptake, the end-result of which is an enhanced capacity to synthesize acetylcholine. This increased acetylcholine synthesis, in turn, appears to translate directly into augmented vesicular storage and release of the neurotransmitter. For instance, not only does NGF treatment reverse lesion-induced reductions in maximal binding densities of the acetylcholine vesicular transport marker [3H]vesamicol, but it also enhances acetylcholine release and turnover rate. NGF treatment also appears to restore the sensitivity of postsynaptic muscarinic receptors to agonist-induced stimulation following partial fimbriectomies.(ABSTRACT TRUNCATED AT 250 WORDS)
最近对神经生长因子（NGF）的研究已经在多种动物模型中确定了这种神经营养因子的药理作用，这些模型模拟了阿尔茨海默病（AD）中出现的一些神经递质缺陷（有关综述，请参阅参考文献7、15、17、19）。基于广泛的药理研究，NGF已被确定为隔海马和基底皮质通路中成年胆碱能神经元的关键维持因子。NGF报道的作用之一是减轻海马结构中病变诱导的突触前和突触后胆碱能标志物及功能的减少。因此，在使用部分穹窿切除术来模拟AD中发生的胆碱能神经变性的研究中，脑室内给予神经生长因子可防止隔区胆碱乙酰转移酶（ChAT）和乙酰胆碱酯酶免疫反应性的丧失，并增加参与神经递质乙酰胆碱合成、储存和释放的多种突触前胆碱能标志物（有关综述，请参阅参考文献7、17、19）。更具体地说，慢性NGF治疗可减轻病变诱导的海马ChAT活性和高亲和力胆碱摄取的降低，其最终结果是增强了合成乙酰胆碱的能力。这种增加的乙酰胆碱合成反过来似乎直接转化为神经递质囊泡储存和释放的增加。例如，NGF治疗不仅能逆转病变诱导的乙酰胆碱囊泡转运标志物[3H]vesamicol最大结合密度的降低，还能提高乙酰胆碱的释放和周转率。NGF治疗似乎还能恢复部分穹窿切除术后突触后毒蕈碱受体对激动剂诱导刺激的敏感性。（摘要截短于250字）
