MODEL FOR COBALAMIN DEFICIENCY

维生素B1缺乏症模型

• 批准号: 3401545
• 负责人: RALPH GREEN
• 金额: $ 13.66万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3401545
• 关键词: analytical method; choline; cofactor; cyanides; diet therapy; disease /disorder model; electron microscopy; electrophysiology; folate; high performance liquid chromatography; histopathology; methionine; methylmalonyl coA epimerase; model design /development; myelinopathy; nervous system disorder; neurochemistry; neuropharmacology; neurotoxins; nitrous oxide; nutrition related tag; pernicious anemia; radiotracer; vitamin B12 deficiency; vitamin metabolism; analytical method; choline; cofactor; cyanides; diet therapy; disease /disorder model; electron microscopy; electrophysiology; folate; high performance liquid chromatography; histopathology; methionine; methylmalonyl coA epimerase; model design /development; myelinopathy; nervous system disorder; neurochemistry; neuropharmacology; neurotoxins; nitrous oxide; nutrition related tag; pernicious anemia; radiotracer; vitamin B12 deficiency; vitamin metabolism

Cobalamin (vitamin B12, Cb1) deficiency can be readily induced in fruit bats (Rousettus aegyptiacus) which are deprived of a dietary source of the vitamin in captivity. They develop an illness with neurological complications, resembling those seen in human pernicious anemia, but without hematological complications. The features of this potential animal model for study of human Cb1 deficiency will be further investigated along the following lines in cb1-deficient and replete bats. Nutritional studies will be extended to compare the effects of cb1, methionine and choline in preventing the neurological changes. Biochemical studies will be carried out to assess whether methylmalonyl CoA mutase or methionine synthetase is the key enzyme in relation to the role of cb1 in the nervous system. The origin and fate of organic acids found in urine in cb1 deficiency will be investigated, and the incorporation of radiolabelled propionate and methylmalonate into myelin lipids will be measured in brain, spinal cord and peripheral nerves. The profile of intracellular forms of cb1 will be analyzed using high performance liquid chromatographpy (hplc). Analysis of nervous system folates will be carried out by hplc and the effects of folate on the neuropathy will be tested. The effects of nitrous oxide, a putative cb1 antagonist, will be compared with the pure nutritional cb1 deficient model. Nerve conduction studies and sensory evoked potentials will be measured in normal and cb1 deficient animals. Structural studies and myelin lipid analysis will be carried out on the brains and spinal cords or bats, including young bats born in captivity. This project seeks to elucidate the metabolic role of cb1 in nervous system tissue and its interaction with other nutrients, notably methionine and folate.

钴胺素（维生素B12，CB1）可能很容易在水果中诱发 蝙蝠（Rousettus aegyptiacus）被剥夺了饮食来源 维生素圈养。 他们患有神经学 并发症，类似于人类有害性贫血的并发症，但 没有血液学并发症。 这种潜在动物的特征 研究人类CB1缺乏症的模型将进一步研究 CB1缺陷型蝙蝠中的以下几条。 营养研究 将扩展以比较CB1，蛋氨酸和胆碱在 防止神经系统变化。 将进行生化研究 评估甲基氨基甲酰基COA突变酶还是蛋氨酸合成酶是 与CB1在神经系统中的作用有关的关键酶。 这 CB1缺乏症中尿液中发现的有机酸的起源和命运将是 调查，并掺入放射性标记的丙酸和 将甲基甲酸甲酯进入髓磷脂脂质将在脑脊髓中测量 和周围神经。 CB1细胞内形式的轮廓将是 使用高性能液相色谱（HPLC）分析。 分析 神经系统的叶状将由HPLC和 将测试神经病的叶酸。 一氧化二氮的作用 假定的CB1拮抗剂将与纯营养CB1进行比较 不足的模型。 神经传导研究和感觉诱发电位 将在正常和CB1缺乏动物中进行测量。 结构研究 并将在大脑和脊柱上进行髓磷脂脂质分析 绳索或蝙蝠，包括被囚禁的年轻蝙蝠。 这个项目寻求 阐明CB1在神经系统组织及其ITS中的代谢作用 与其他营养素的相互作用，特别是蛋氨酸和叶酸。