Behavioral abnormalities and reduced norepinephrine in EP4 receptor-associated protein (EPRAP)-deficient mice
Behavioral abnormalities and reduced norepinephrine in EP4 receptor-associated protein (EPRAP)-deficient mice
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DOI：
10.1016/j.bbrc.2017.03.095
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发表时间：
2017-04-29
影响因子：
3.1
通讯作者：
Minami, Manabu
中科院分区：
文献类型：
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作者：
Fujikawa, Risako;Higuchi, Sei;Minami, Manabu
EP4受体相关蛋白（EP4 receptor-associated protein， EPRAP）是一种新发现的调控巨噬细胞活化的分子。我们最近证明了EPRAP在小鼠大脑中的存在；然而，关于EPRAP在该组织中的功能知之甚少。因此，我们利用小鼠行为分析研究了EPRAP在行为和情绪中的作用。在这项研究中，我们对eprap缺陷（KO）小鼠和野生型C57BL/6 （WT）小鼠进行了一系列行为测试。EPRAP-KO小鼠在吊丝试验中倾向于有较短的跌倒潜伏期，但神经肌肉力量正常。EPRAP-KO小鼠表现出较高的惊吓反应和减少的脉冲前抑制。与WT小鼠相比，EPRAP-KO小鼠在强迫游泳试验中抑郁样行为增加。这些异常行为部分模仿了抑郁症、注意力缺陷多动障碍（ADHD）和精神分裂症的症状。哌醋甲酯给药对EPRAP-KO小鼠运动活动的促进作用低于WT小鼠。最后，EPRAP-KO小鼠脑内去甲肾上腺素水平降低。EPRAP-KO小鼠的这些行为异常可能是单胺功能障碍，特别是去甲肾上腺素的功能障碍造成的。我们的研究结果表明EPRAP参与了多种行为障碍的发病机制。(C) 2017爱思唯尔公司版权所有。
EP4 receptor-associated protein (EPRAP) is a newly identified molecule that regulates macrophage activation. We recently demonstrated the presence of EPRAP in the mice brain; however, little is known about the function of EPRAP in this tissue. Therefore, we investigated the role of EPRAP in behavior and emotion using behavioral analysis in mice. In this study, we subjected EPRAP-deficient (KO) mice and wild-type C57BL/6 (WT) mice to a battery of behavioral tests. EPRAP-KO mice tended to have shorter latencies to fall in the wire hang test, but had normal neuromuscular strength. EPRAP-KO mice exhibited elevated startle responses and reduced pre-pulse inhibition. Compared with WT mice, EPRAP-KO mice increased depression-like behavior in the forced swim test. These abnormal behaviors partially mimic symptoms of depression, attention deficit hyperactivity disorder (ADHD) and schizophrenia. Methylphenidate administration increased locomotor activity less in EPRAP-KO mice than in WT mice. Finally, levels of norepinephrine were reduced in the EPRAP-KO mouser brain. These behavioral abnormalities in EPRAP-KO mice may result from the dysfunction of monoamines, in particular, norepinephrine. Our results suggest that EPRAP participates in the pathogenesis of various behavioral disorders. (C) 2017 Elsevier Inc. All rights reserved.