Elucidation of biological basis of autism as fatty acid metabolic disease

阐明自闭症作为脂肪酸代谢疾病的生物学基础

• 批准号: 21200014
• 负责人: MATSUZAKI Hideo
• 金额: $ 17.64万
• 依托单位: Hamamatsu University School of Medicine (2010-2011)Osaka University (2009)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21200014/
• 关键词: 自閉症; 脂質代謝異常; 発達

In this project, we were focusing on impaired Very Low Density Lipoprotein (VLDL) lipid fraction in serum of individuals with autism. Then, we examined the serum levels of fatty acid composition, autistic animal models based on the lipid profile, imaging analyze and a novel therapy method of autism by using the autistic animal model. To identify causal fatty acid of VLDL-specific lipid profile in autism, we analyzed fatty acid composition by GC-MS, which resulted in impairment of some fatty acids including omega-6. Next, we identified that CD38KO mice showed impairment of VLDL fraction and omega-6 fatty acid like autistic human subject, and found that feeding challenge of omega-6 fatty acid could rescue impairment of social recognition behavior in CD38KO mice immediately after birth. In VLDL Receptor transgenic rat (VLDLR-Tg), we examined behavior test and found that the rat showed hyperactivity and an entire impairment of arachidonic acid distribution in tissues of VLDLR-Tg.

在这个项目中，我们关注的是自闭症患者血清中极低密度脂蛋白(VLDL)受损的脂类成分。然后，我们检测了血清脂肪酸组成水平、基于血脂谱的自闭症动物模型、影像分析以及利用自闭症动物模型治疗自闭症的新方法。为了确定自闭症患者极低密度脂蛋白特异性脂谱的原因脂肪酸，我们用GC-MS分析了导致包括omega-6在内的一些脂肪酸受损的脂肪酸组成。接下来，我们发现CD38KO小鼠表现出类似自闭症人类受试者的VLDL组分和omega-6脂肪酸的损害，并且发现omega-6脂肪酸的喂养挑战可以在出生后立即修复CD38KO小鼠的社会识别行为的损害。在VLDLR转基因大鼠(VLDLR-TG)中，我们进行了行为学测试，发现VLDLR-TG大鼠表现出多动，花生四烯酸在VLDLR-TG组织中的分布完全受损。

项目成果

Serum levels of anterior pituitary hormones in children with autism

自闭症儿童血清垂体前叶激素水平

• 发表时间: 2011
• 作者: Matsuzaki H;Iwata K;Mori N
• 通讯作者: Mori N

Serum adipokine levels in children with autism

自闭症儿童血清脂肪因子水平

• 发表时间: 2010
• 作者: H.Chinen;Y.Pihosh;K.Mawatari;T.Kitamori;Matsuzaki H
• 通讯作者: Matsuzaki H

高機能自閉症児に認められる特異的代謝異常の医療応用

高功能自闭症儿童中发现的特定代谢异常的医学应用

• 发表时间: 2009
• 作者: 油井邦雄;Declan Murphy;濱川浩;松崎秀夫
• 通讯作者: 松崎秀夫

A perspective of biological marker research for Autism.

自闭症生物标志物研究的视角。

• 发表时间: 2009
• 作者: 小柴満美子;妹尾綾;池上健太郎;野嶋奈津紀;大原高秋;藤井健志;鈴木将登;中村暢文;中村俊;入交眞巳;松浦晶央;甫立孝一;松崎秀夫;T.Kitamori;松崎秀夫
• 通讯作者: 松崎秀夫

A perspective of biological marker research for Autism

自闭症生物标志物研究的视角

• 发表时间: 2009
• 作者: 小原早綾;妹尾綾;乙幡和重;藤井健志;中村俊;小柴満美子;Matsuzaki H
• 通讯作者: Matsuzaki H