Relaxin‐3 null mutation mice display a circadian hypoactivity phenotype
Relaxin‐3 null mutation mice display a circadian hypoactivity phenotype
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DOI：
10.1111/j.1601-183x.2011.00730.x
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发表时间：
2012-02
期刊：
影响因子：
3.5
通讯作者：
Craig M. Smith;I. T. Hosken;Steve W. Sutton;Andrew J. Lawrence;A. L. Gundlach
中科院分区：
文献类型：
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作者：
Craig M. Smith;I. T. Hosken;Steve W. Sutton;Andrew J. Lawrence;A. L. Gundlach
表征唤醒和昼夜睡眠/觉醒模式背后的神经回路和神经递质是神经科学研究的一个重要目标，对理解人类精神疾病（如重度抑郁症）具有潜在意义。最近的解剖学和功能研究表明，松弛素-3神经元及其上行投射通过对关键皮层、边缘系统和下丘脑回路的作用来促进这些功能。本研究报告了C57 BL/6 J回交松弛素-3基因敲除（KO）小鼠的行为表型。对成年、雄性和雌性松弛素-3 KO和野生型（WT）同窝小鼠队列进行一系列行为测试，以评估感觉运动功能和复杂行为。在运动协调、空间记忆、感觉运动门控、焦虑样行为或新环境中的运动行为中未检测到明显的缺陷;在对慢性应激方案的反应中未观察到明显的基因型差异。然而，值得注意的是，与WT小鼠相比，松弛素-3 KO小鼠在黑暗/活动期期间显示出强烈的活动减退，当提供自由的笼舍进入自愿跑步轮时。这种生理机能减退反映在跑步轮上花费的时间和行驶的距离减少，加上不动时间的增加，可能反映了睡眠的增加。总的来说，这些研究支持松弛素-3信号在控制觉醒和睡眠/觉醒中的作用，并将松弛素-3 KO小鼠确定为进一步研究这种作用的有用模型。
Characterizing the neurocircuits and neurotransmitters that underlie arousal and circadian sleep/wake patterns is an important goal of neuroscience research, with potential implications for understanding human mental illnesses, such as major depression. Recent anatomical and functional studies suggest that relaxin‐3 neurons and their ascending projections contribute to these functions via actions on key cortical, limbic and hypothalamic circuits. This study reports the behavioral phenotype of C57BL/6J backcrossed relaxin‐3 knockout (KO) mice. Cohorts of adult, male and female relaxin‐3 KO and wild‐type (WT) littermate mice were subjected to a battery of behavioral tests to assess sensorimotor function and complex behavior. No overt deficits were detected in motor‐coordination, spatial memory, sensorimotor gating, anxiety‐like behavior or locomotor behavior in novel environments; and no marked genotype differences were observed in response to a chronic stress protocol. Notably however, compared to WT mice, relaxin‐3 KO mice displayed robust hypoactivity during the dark/active phase when provided with free home‐cage access to voluntary running wheels. This circadian hypoactivity was reflected by reduced time spent and distance traveled on running wheels, coupled with an increase in the time spent immobile, possibly reflecting increased sleeping. Overall, these studies support a role for relaxin‐3 signaling in the control of arousal and sleep/wakefulness, and identify the relaxin‐3 KO mouse as a useful model to study this role further.