Peptidomic Analysis Reveals Seasonal Neuropeptide and Peptide Hormone Changes in the Hypothalamus and Pituitary of a Hibernating Mammal
Peptidomic Analysis Reveals Seasonal Neuropeptide and Peptide Hormone Changes in the Hypothalamus and Pituitary of a Hibernating Mammal
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DOI：
10.1021/acschemneuro.3c00268
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发表时间：
2023-07-03
影响因子：
5
通讯作者：
Checco，James W.
中科院分区：
文献类型：
--
作者：
Mousavi，Somayeh;Qiu，Haowen;Checco，James W.
在冬天，冬眠的哺乳动物经历了极端的生理变化，这使得它们在没有食物的情况下可以存活几个月。这些动物进入麻木状态，其特征是新陈代谢减慢，体温接近冰点，心率急剧下降。这一调控的神经化学基础在很大程度上是未知的。根据先前的证据表明，富含多肽的下丘脑在冬眠中起着关键作用，我们假设在昏迷/觉醒周期中，特定的细胞-细胞信号肽(神经肽和多肽激素)的变化是生理变化的基础。为了验证这一假设，我们使用了一种基于质谱学的多肽方法来研究冬眠哺乳动物十三行地鼠(Ictidomys Tridecemlineatus)下丘脑和脑垂体中内源性多肽的季节性变化。在脑垂体中，我们观察到了动物在10月份准备昏迷、3月份离开昏迷以及从春季(3月)到秋季(8月)的过程中几种不同的多肽激素的变化。在下丘脑，我们观察到10月份(昏迷前)神经肽的总体增加，随着动物进入昏迷而减少，在常温的间歇性觉醒期间神经肽的子集增加。观察到摄食调节性多肽、阿片肽和几种功能不明确的多肽的显著变化。总体而言，我们的研究提供了对哺乳动物冬眠期间下丘脑和脑垂体内源性多肽变化的关键洞察，这些变化不是通过转录测量获得的。了解冬眠表型的分子基础可能会为未来采用类似冬眠的策略保存器官、对抗肥胖和治疗中风铺平道路。
During the winter, hibernating mammals undergo extreme changes in physiology, which allow them to survive several months without access to food. These animals enter a state of torpor, which is characterized by decreased metabolism, near-freezing body temperatures, and a dramatically reduced heart rate. The neurochemical basis of this regulation is largely unknown. Based on prior evidence suggesting that the peptide-rich hypothalamus plays critical roles in hibernation, we hypothesized that changes in specific cell–cell signaling peptides (neuropeptides and peptide hormones) underlie physiological changes during torpor/arousal cycles. To test this hypothesis, we used a mass spectrometry-based peptidomics approach to examine seasonal changes of endogenous peptides that occur in the hypothalamus and pituitary of a model hibernating mammal, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). In the pituitary, we observed changes in several distinct peptide hormones as animals prepared for torpor in October, exited torpor in March, and progressed from spring (March) to fall (August). In the hypothalamus, we observed an overall increase in neuropeptides in October (pre-torpor), a decrease as the animal entered torpor, and an increase in a subset of neuropeptides during normothermic interbout arousals. Notable changes were observed for feeding regulatory peptides, opioid peptides, and several peptides without well-established functions. Overall, our study provides critical insight into changes in endogenous peptides in the hypothalamus and pituitary during mammalian hibernation that were not available from transcriptomic measurements. Understanding the molecular basis of the hibernation phenotype may pave the way for future efforts to employ hibernation-like strategies for organ preservation, combating obesity, and treatment of stroke.