Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis
Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis
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DOI：
10.1073/pnas.1003969107
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发表时间：
2010-05-04
影响因子：
11.1
通讯作者：
Chen, Alon
中科院分区：
文献类型：
--
作者：
Kuperman, Yael;Issler, Orna;Chen, Alon
为了应对生理或心理挑战，大脑激活与代谢和情绪输出相关的行为和神经内分泌系统，旨在适应需求。然而，这些生理反应对挑战的整合失调可能会产生严重的心理和生理后果，并且应激反应的不适当调节、不成比例的强度或慢性或不可逆的激活与情绪和代谢紊乱的病因学和病理生理学有关。使用转基因小鼠模型和慢病毒方法，我们证明了下丘脑神经肽 Urocortin-3（2 型促肾上腺皮质激素释放因子受体的特异性配体）参与调节分别负责焦虑样行为和代谢功能的间隔核和下丘脑核。这些结果将 Urocortin-3 定位为一种连接压力引起的焦虑和能量稳态的神经调节剂，并为更好地理解介导压力、情绪和代谢紊乱之间相互关系的机制铺平了道路。
In response to physiological or psychological challenges, the brain activates behavioral and neuroendocrine systems linked to both metabolic and emotional outputs designed to adapt to the demand. However, dysregulation of integration of these physiological responses to challenge can have severe psychological and physiological consequences, and inappropriate regulation, disproportional intensity, or chronic or irreversible activation of the stress response is linked to the etiology and pathophysiology of mood and metabolic disorders. Using a transgenic mouse model and lentiviral approach, we demonstrate the involvement of the hypothalamic neuropeptide Urocortin-3, a specific ligand for the type-2 corticotropin-releasing factor receptor, in modulating septal and hypothalamic nuclei responsible for anxiety-like behaviors and metabolic functions, respectively. These results position Urocortin-3 as a neuro-modulator linking stress-induced anxiety and energy homeostasis and pave the way toward better understanding of the mechanisms that mediate the reciprocal relationships between stress, mood and metabolic disorders.