Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour
Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour
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DOI：
10.1038/ncomms6759
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发表时间：
2014-12-01
影响因子：
16.6
通讯作者：
Burris, Thomas P.
中科院分区：
文献类型：
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作者：
Banerjee, Subhashis;Wang, Yongjun;Burris, Thomas P.
直接调节关键时钟蛋白活性的合成药物样分子提供了直接调节内源性昼夜节律和治疗与时钟功能障碍相关的疾病的潜力。在这里，我们证明了合成配体靶向哺乳动物生物钟的关键组成部分，即核受体REV-ERB α和β，调节小鼠的睡眠结构和情绪行为。REV-ERB激动剂诱导觉醒，减少REM和慢波睡眠。有趣的是，REV-ERB激动剂也能减少焦虑样行为。这些数据与REV-ERB β缺失小鼠的焦虑样行为增加一致，REV-ERB激动剂对小鼠没有影响。这些结果表明，REV-ERB的药理靶向可能会导致治疗睡眠障碍和焦虑的新疗法的发展。
Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the potential to directly modulate the endogenous circadian rhythm and treat diseases associated with clock dysfunction. Here we demonstrate that synthetic ligands targeting a key component of the mammalian clock, the nuclear receptors REV-ERB alpha and beta, regulate sleep architecture and emotional behaviour in mice. REV-ERB agonists induce wakefulness and reduce REM and slow-wave sleep. Interestingly, REV-ERB agonists also reduce anxiety-like behaviour. These data are consistent with increased anxiety-like behaviour of REV-ERB beta-null mice, in which REV-ERB agonists have no effect. These results indicate that pharmacological targeting of REV-ERB may lead to the development of novel therapeutics to treat sleep disorders and anxiety.