TARGET-DERIVED NEURONOTROPHIC FACTORS

神经生长因子是外周血细胞的靶源性蛋白 交感神经系统和感觉神经系统。类似的营养因子已经被 推测存在于中枢神经系统神经元。身份识别 一种神经营养因子参与胆碱能隔-海马区 路径就是本研究项目的主题。常规和 解决这个问题的分子生物学方法已经开始。 大鼠胚胎隔区神经元的原代分离培养 建立一种监测胆碱能活性的检测系统 营养因子。这些培养的细胞对胆碱有摄取系统。 这是时间、温度和部分钠相关的。初步 结果还表明，乙酰胆碱是由提取的胆碱合成的 在牢房旁边。因此，隔膜细胞的培养是一种合适的系统 损伤后胆碱能营养因子(S)的测定 隔-海马区通路。一种分子生物学方法也是 被用来识别并最终表征营养因子。 从海马区mRNA和DNA合成了互补DNA(CDNAs) 将用于cdna-mrna杂交以识别由损伤引起的和 新的信使核糖核酸物种。注射含有mRNA片段的青蛙卵母细胞将 作为体外翻译系统和编码的营养蛋白 将通过胆碱能参数的变化来检测 培养的隔细胞。一种新的胆碱能基因的鉴定和克隆 神经营养因子可能导致新的治疗方法 胆碱能成分改变的神经系统疾病，如 阿尔茨海默氏症。

Nerve growth factor is a target-derived protein for the peripheral sympathetic and sensory nervous system. Similar trophic factors have been postulated to exist for central nervous system neurons. The identification of a neurotrophic factor involved in the cholinergic septo-hippocampal pathway is the subject of this research project. Conventional and molecular biological approaches to this problem have been initiated. Primary dissociated cultures of rat fetal septal area neurons have been established as an assay system to monitor the activity of the cholinergic trophic factor. These cultured cells have an uptake system for choline that is time-, temperature-, and partially Na-dependent. Preliminary results also show that acetylcholine is synthesized from the choline taken up by the cells. Thus, septal cells in culture are a suitable system to assay for cholinergic trophic factor(s) that may be induced by lesions of the septo-hippocampal pathway. A molecular biological approach is also being used to identify and, ultimately, characterize the trophic factor. Complementary DNA (cDNA) has been synthesized from hippocampal mRNA and will be used in cDNA-mRNA hybridizations to identify lesion-induced and novel mRNA species. Injection of frog oocytes with mRNA fractions will serve as an in vitro translation system and the encoded trophic proteins will be assayed by alterations in the cholinergic parameters of the cultured septal cells. Identification and cloning of a novel cholinergic neuronotrophic factor may lead to new therapeutic approaches to neurological diseases with an altered cholinergic component, such as Alzheimer's disease.