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

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.

水果中很容易诱发钴胺素（维生素 B12、Cb1）缺乏 蝙蝠（Rousettus aegyptiacus）被剥夺了饮食来源 圈养的维生素。 他们患有神经系统疾病 并发症，类似于人类恶性贫血中所见的并发症，但是 无血液学并发症。 这种潜在动物的特征 人类 Cb1 缺乏症研究模型将进一步研究 缺乏 cb1 和充满 cb1 的蝙蝠中的以下细胞系。 营养研究 将扩展以比较 cb1、蛋氨酸和胆碱在 预防神经系统变化。 将进行生化研究 评估甲基丙二酰辅酶A变位酶或蛋氨酸合成酶是否 与 cb1 在神经系统中的作用有关的关键酶。 这 cb1 缺乏症患者尿液中有机酸的来源和归宿将是 进行了研究，并掺入了放射性标记的丙酸盐和 丙二酸甲酯转化为髓磷脂脂质将在大脑、脊髓中进行测量 和周围神经。 cb1 的细胞内形式的概况将是 使用高效液相色谱法（hplc）进行分析。 分析 神经系统叶酸将通过 hplc 进行，并影响 叶酸对神经病变的影响将得到测试。 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 模型有缺陷。 神经传导研究和感觉诱发电位 将在正常和 cb1 缺陷动物中进行测量。 结构研究 将对大脑和脊髓进行髓磷脂脂质分析 绳索或蝙蝠，包括圈养中出生的幼蝙蝠。 该项目寻求 阐明cb1在神经系统组织中的代谢作用及其 与其他营养素，特别是蛋氨酸和叶酸的相互作用。