Functional analysis of fatty acid binding proteins in the brain

大脑中脂肪酸结合蛋白的功能分析

• 批准号: 14580720
• 负责人: OWADA Yuji
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580720/
• 关键词: fatty acid binding protein; TEWL; radial glia; astrocyte; thymic epithelial cell; IL12; PALS; マウス; LTP; 記憶; 学習; ドコサヘキサエン酸; 脳

It was shown that fatty acids, especially docosahexiaenoic acid and arachidonic acid, are important in the verious brain functions, including learning and memory functions. Brain type-fatty acid binding protein (B--FABP) belongs to a family of intracellular lipid binding proteins. B-FABP exhibits a higher binding affinity to docosahexaenoic acid (DNA) whose effect on learning and memory function has been documented, and it is localized in the ventricular germinal cells in embryonic brain and astroglia in adult brain of rodents. The present study generated mice harboring a null mutation in the B-FABP gene and the phenotype analysis of the gene-knockout mice exhibited the impaired learning, and memory function. and the decreased content of DNA in their brain without detection of any histological changes in the brain. Furthermore, the response of NMDA receptor-mediated current to DNA in isolated hippocampal neurons from the B-FABP mutant mice was significantly decreased in comparison with that of wild mice. These data indicate that B-FABP in the glia is intimately involved in the well-known effect of DHA on learning and memory.

研究表明，脂肪酸，特别是二十二碳六烯酸和花生四烯酸，在包括学习和记忆功能在内的多种大脑功能中都是重要的。脑型脂肪酸结合蛋白(B-FABP)属于细胞内脂结合蛋白家族。B-FABP与二十二碳六烯酸(DNA)具有较高的亲和力，其对学习记忆功能的影响已被证实，并定位于啮齿动物胚胎脑室生发细胞和成年脑星形胶质细胞。本研究产生了B-FABP基因零突变的小鼠，基因敲除小鼠的表型分析显示学习和记忆功能受损。以及他们大脑中DNA含量的下降，而没有检测到大脑中的任何组织学变化。此外，B-FABP突变小鼠分离的海马神经元对DNA的NMDA受体介导的电流对DNA的反应明显低于野生小鼠。这些数据表明，胶质细胞中的B-FABP与DHA对学习和记忆的众所周知的影响密切相关。

项目成果

Takano N., Owada Y.et al.: "Cloning and characterization of a novel variant of mouse M-rdgBB proteins and its localization・・・"J. Neurochem. 84. 829-839 (2002)

Takano N.、Owada Y. 等人：“小鼠 M-rdgBB 蛋白新变体的克隆和表征及其定位......”J. Neurochem 84. 829-839 (2002)

Y.Owada, H.Kondo: "Cellular Proteins and their Fatty acids in Health and Disease"Duttaroy AK and Spener F eds, Wiley-VCH. 460 (2003)

Y.Owada、H.Kondo：“健康和疾病中的细胞蛋白质及其脂肪酸”Duttaroy AK 和 Spener F eds，Wiley-VCH。

Owada, Y. et al.: "Analysis an the phenotype of E-FABP gene knockout mice"Mol. Cell. Biochemistry. 239. 83-86 (2002)

Owada, Y. 等：“E-FABP 基因敲除小鼠的表型分析”Mol。

N Takano, Y Owada, H Kondo: "Cloning and characterization of a novel variant of M-rdgBs"J Neurochem. 84. 829-839 (2003)

N Takano、Y Owada、H Kondo：“M-rdgB 新型变体的克隆和表征”J Neurochem。

N Takano, Y Owada, H Kondo: "Cloning and characterization of a novel variant of mouse M-rdfBβ, and its mRNA localization in mouse brain in comparison with other M-rdgBs"Journal of Neurochemistry. 84. 829-839 (2003)

N Takano、Y Owada、H Kondo：“小鼠 M-rdfBβ 新型变体的克隆和表征，以及与其他 M-rdgB 相比其在小鼠大脑中的 mRNA 定位”《神经化学杂志》84. 829-839 (2003)。