Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice
Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice
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DOI：
10.1111/j.1460-9568.2004.03749.x
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Shibata, S
中科院分区：
文献类型：
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作者：
Akiyama, M;Yuasa, T;Shibata, S
每日限食（RF）产生预期的自发活动节律，并独立于位于视交叉上核（SCN）的中枢起搏器，携带外周分子振荡器。由于食欲素（hypocretins）是协调睡眠/觉醒模式和动机行为（如寻找食物）的神经肽，我们研究了食欲素在RF诱导的食物预期活动（FAA）中的参与。每日RF移动的时钟控制基因mDbp在大脑皮层和尾壳核，但不是在SCN的mRNA的节奏。在这些实验条件下，下丘脑外侧区（LHA）的前原食欲素mRNA和食欲素A的免疫反应性没有表现出每日变化。禁食增加食欲素A-ir细胞的数量，而RF没有。但RF使增食欲素神经元Fos表达的高峰由夜间移至白天。在RF条件下，食欲素/共济失调蛋白-3转基因小鼠中食欲素神经元的基因消融严重减少了FAA的形成。在食欲素/共济失调蛋白-3小鼠的前脑中，mNpas 2 mRNA的表达减少，mNpas 2 mRNA是一种转录因子，被认为参与调节食物可消化振荡器以及mPer 1和mBmal 1 mRNA。基于这些结果，我们认为LHA中的食欲素神经元的活性有助于FAA的促进和维持。
Daily restricted feeding (RF) produces an anticipatory locomotor activity rhythm and entrains the peripheral molecular oscillator independently of the central pacemaker located in the suprachiasmatic nucleus (SCN). As orexins (hypocretins) are neuropeptides that coordinate sleep/wake patterns and motivated behaviours, such as food seeking, we studied the involvement of orexin in the food anticipatory activity (FAA) induced by RF. Daily RF shifted the mRNA rhythm of a clock-controlled gene mDbp in the cerebral cortex and caudate putamen but not in the SCN. Under these experimental conditions, prepro-orexin mRNA and orexin A immunoreactivity in the lateral hypothalamic area (LHA) did not show daily variation. Fasting increased the number of orexin A-ir cells, while RF did not. However, RF shifted the peak of Fos expression of the orexin neurons from night to day. Genetic ablation of orexin neurons in orexin/ataxin-3 transgenic mice severely reduced the formation of FAA under RF conditions. The expression of mNpas2 mRNA, a transcription factor thought to be involved in regulation of the food entrainable oscillator as well as mPer1 and mBmal1 mRNA, was reduced in the forebrain of orexin/ataxin-3 mice. Based on these results, we suggest that activity of the orexin neuron in the LHA contributes to the promotion and maintenance of FAA.