TARGET-DERIVED NEURONOTROPHIC FACTORS

靶标衍生的神经营养因子

• 批准号: 4696424
• 负责人: B WISE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696424
• 关键词: Alzheimer's disease; acetylcholine; brain septal area; choline; cholinergic agents; complementary DNA; embryo /fetus tissue /cell culture; experimental brain lesion; genetic manipulation; genetic translation; messenger RNA; molecular biology; molecular cloning; neurons; neurophysiology; parasympathetic nervous system

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.

神经生长因子是外周神经的靶标衍生蛋白 交感神经和感觉神经系统。 类似的营养因子 假设中枢神经系统神经元存在。 鉴定 涉及胆碱能间隔海马的神经营养因子 途径是本研究项目的主题。 常规和 已经开始采用分子生物学方法来解决这个问题。 大鼠胎儿间隔区神经元的原代分离培养物已被 建立监测胆碱能活性的测定系统 营养因子。 这些培养细胞具有胆碱摄取系统 这与时间、温度和部分 Na 相关。 初步的 结果还表明，乙酰胆碱是由摄入的胆碱合成的。 由细胞向上。 因此，培养中的隔膜细胞是一个合适的系统 检测可能由损伤引起的胆碱能营养因子 隔海马通路。 分子生物学方法也 用于识别并最终表征营养因子。 互补 DNA (cDNA) 已由海马 mRNA 合成， 将用于 cDNA-mRNA 杂交，以鉴定损伤诱导的和 新的 mRNA 种类。 将 mRNA 片段注射到青蛙卵母细胞中 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进行测定 培养的隔膜细胞。 新型胆碱能药物的鉴定和克隆 神经营养因子可能会带来新的治疗方法 胆碱能成分改变的神经系统疾病，例如 阿尔茨海默病。