Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities
Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities
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DOI：
10.1038/mp.2008.97
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发表时间：
2010-02-01
影响因子：
11
通讯作者：
Aruga, J.
中科院分区：
文献类型：
--
作者：
Katayama, K.;Yamada, K.;Aruga, J.
抽动秽语综合征和拔毛癖患者中发现了 SLITRK1 突变。 SLITRK1 编码一种含有富含亮氨酸重复序列的跨膜蛋白，该蛋白主要在神经系统中产生。然而，这种蛋白质的作用很大程度上未知，除了它可以在体外调节神经突生长。为了阐明 Slitrk1 在体内的作用，我们培育了 Slitrk1 敲除小鼠并分析了它们的行为和神经化学表型。 Slitrk1缺陷小鼠在高架十字迷宫测试中表现出焦虑样行为，在强迫游泳和悬尾测试中表现出不动时间增加。神经化学分析显示，Slitrk1 敲除小鼠的去甲肾上腺素及其代谢物 3-甲氧基-4-羟基苯基乙二醇的水平增加。可乐定（一种常用于治疗图雷特氏综合症患者的 α2-肾上腺素能激动剂）可减轻 Slitrk1 缺陷小鼠在高架十字迷宫测试中的焦虑样行为。这些结果使我们得出结论，去甲肾上腺素能机制与 Slitrk1 缺陷小鼠的行为异常有关。 Slitrk1 功能障碍导致的焦虑加剧可能导致抽动秽语综合征和拔毛癖等神经精神疾病的发病机制。分子精神病学 (2010) 15, 177-184; doi：10.1038/mp.2008.97； 2008 年 9 月 16 日在线发布
Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha 2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plusmaze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania. Molecular Psychiatry (2010) 15, 177-184; doi: 10.1038/mp.2008.97; published online 16 September 2008