Impairment of neuropsychological behaviors in ganglioside GM3-knockout mice
Impairment of neuropsychological behaviors in ganglioside GM3-knockout mice
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DOI：
10.1016/j.bbrc.2011.02.071
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发表时间：
2011-03-25
影响因子：
3.1
通讯作者：
Yamashita, Tadashi
中科院分区：
文献类型：
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作者：
Niimi, Kimie;Nishioka, Chieko;Yamashita, Tadashi
神经节苷脂 GM3 合酶 (SAT-I) 由单拷贝基因编码，是合成复杂神经节苷脂的主要糖基转移酶。尽管其表达在大脑的早期胚胎发育和出生后发育和成熟过程中受到严格控制，但神经节苷脂GM3在神经元功能调节中的生理作用尚未阐明。在本研究中，我们检查了幼年 GM3 敲除 (GM3-KO) 小鼠的运动活动、认知和情绪行为以及药物管理。 GM3-KO雄性和雌性小鼠在运动活动测试、Y迷宫测试和高架十字迷宫测试中表现出过度活跃。在V迷宫测试中，GM3-KO雄性小鼠的自发交替行为明显少于野生型小鼠。在高架十字迷宫测试中，GM3-KO雄性小鼠张开双臂的时间明显高于性别匹配的野生型小鼠。相比之下，在这些测试中GM3-KO和野生型雌性小鼠之间没有显着差异。因此，幼年 GM3-KO 小鼠表现出类似于注意力缺陷多动障碍 (ADHD) 的性别特异性表型，即多动、注意力下降和冲动行为增加。然而，给予盐酸哌甲酯 (MPH) 并不能改善雄性或雌性 GM3-KO 小鼠的多动症。尽管这些数据表明神经节苷脂 GM3 与 ADHD 相关，并且 MPH（治疗 ADHD 药物的首选精神兴奋剂）无效，但我们的研究表明，幼年 GM3-KO 小鼠是神经心理学研究的有用工具。 (C) 2011 Elsevier Inc. 保留所有权利。
The ganglioside GM3 synthase (SAT-I), encoded by a single-copy gene, is a primary glycosyltransferase for the synthesis of complex gangliosides. Although its expression is tightly controlled during early embryo development and postnatal development and maturation in the brain, the physiological role of ganglioside GM3 in the regulation of neuronal functions has not been elucidated. In the present study, we examined motor activity, cognitive and emotional behaviors, and drug administration in juvenile GM3-knockout (GM3-KO) mice. GM3-KO male and female mice showed hyperactivity in the motor activity test, Y-maze test, and elevated plus maze test. In the V-maze test, there was significantly less spontaneous alternation behavior in GM3-KO male mice than in wild-type mice. In the elevated plus maze test, the amount of time spent on the open arms by GM3-KO male mice was significantly higher than that of sex-matched wild-type mice. In contrast, there was no significant difference between GM3-KO and wild-type female mice in these tests. Thus, juvenile GM3-KO mice show gender-specific phenotypes resembling attention-deficit hyperactivity disorder (ADHD), namely hyperactivity, reduced attention, and increased impulsive behaviors. However, administration of methylphenidate hydrochloride (MPH) did not ameliorate hyperactivity in either male or female GM3-KO mice. Although these data demonstrate the involvement of ganglioside GM3 in ADHD and the ineffectiveness of MPH, the first-choice psychostimulant for ADHD medication, our studies indicate that juvenile GM3-KO mice are a useful tool for neuropsychological studies. (C) 2011 Elsevier Inc. All rights reserved.