Reduced motor and sensory functions and emotional response in GM3-only mice: Emergence from early stage of life and exacerbation with aging
Reduced motor and sensory functions and emotional response in GM3-only mice: Emergence from early stage of life and exacerbation with aging
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DOI：
10.1016/j.bbr.2008.10.024
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发表时间：
2009-03-02
影响因子：
2.7
通讯作者：
Furukawa, Koichi
中科院分区：
文献类型：
--
作者：
Tajima, Orie;Egashira, Nobuaki;Furukawa, Koichi
含唾液酸的鞘糖脂（神经节苷脂）被认为在神经组织的调节和保护中发挥作用。为了阐明它们在体内神经系统中的功能，产生GM 2/GD 2合酶和GD 3合酶基因的双敲除（DKO）小鼠，并分析异常行为。突变小鼠表现出减少的重量和圆形的整个大脑，逐渐出现与老化，并显示运动功能障碍的足迹，牵引，开放领域，和24小时的运动活动测试。感觉功能在冯弗雷和热板测试中也降低，在声学惊吓反应测试中大大降低。对于情绪行为，恐惧反应明显减少。在出生后10-23周检查的年轻突变小鼠中发现了许多神经元功能障碍，这些功能障碍随着年龄的增长而加剧。这些结果表明，缺乏神经节苷脂以外的GM 3诱导严重的神经元变性在生命的早期阶段，和复杂的神经节苷脂的表达是必不可少的，以维持整个生命的神经系统的完整性。(C)2008 Elsevier B. V.保留所有权利。
Sialic acid-containing glycosphingolipids (gangliosides) have been believed to play a role in the regulation and protection of nervous tissues. To clarify their function in the nervous system in vivo, double knockout (DKO) mice of GM2/GD2 synthase and GD3 synthase genes were generated and abnormal behaviors were analyzed. Mutant mice exhibited reduced weight and a round shape of the whole brain that progressively emerged with aging, and displayed motor dysfunction in the footprint, traction, open-field, and 24 h locomotion activity tests. Sensory functions were also reduced in the von Frey and hot plate tests and greatly reduced in the acoustic startle response test. For emotional behavior, fear response was clearly decreased. Numerous neuronal dysfunctions were found even in younger mutant mice examined at 10-23 weeks after birth, which were exacerbated with aging. These results suggest that a lack of gangliosides other than GM3 induces severe neuronal degeneration in the early stage of life, and that the expression of complex gangliosides is essential to maintain the integrity of the nervous system throughout life. (C) 2008 Elsevier B.V. All rights reserved.