Hibernating animals demonstrate a remarkable ability to withstand extreme physiological brain changes without triggering adverse neuroinflammatory responses. While hibernators may offer valuable insights into the neuroprotective mechanisms inherent to hibernation, studies using such species are constrained by the limited availability of molecular tools. Laboratory mice may serve as an alternative, entering states of hypometabolism and hypothermia similar to the torpor observed in hibernation when faced with energy shortage. Notably, prolonged calorie restriction (CR) induces serial daily torpor patterns in mice, comparable to species that utilize daily hibernation. Here, we examined the neuroinflammatory response in the hippocampus of male C57BL/6 mice undergoing serial daily torpor induced by a 30% CR for 4 weeks. During daily torpor episodes, CR mice exhibited transient increases in TNF-α mRNA expression, which normalized upon arousal. Concurrently, the CA1 region of the hippocampus showed persistent morphological changes in microglia, characterized by reduced cell branching, decreased cell complexity and altered shape. Importantly, these morphological changes were not accompanied by evident signs of astrogliosis or oxidative stress, typically associated with detrimental neuroinflammation. Collectively, the adaptive nature of the brain’s inflammatory response to CR-induced torpor in mice parallels observations in hibernators, highlighting its value for studying the mechanisms of brain resilience during torpor. Such insights could pave the way for novel therapeutic interventions in stroke and neurodegenerative disorders in humans.

中文翻译：

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热量限制引起的连续每日麻木状态小鼠的海马神经免疫反应

冬眠动物表现出非凡的能力，能够承受极端的大脑生理变化，而不会引发不良的神经炎症反应。虽然冬眠者可能为冬眠固有的神经保护机制提供有价值的见解，但使用此类物种的研究受到分子工具可用性有限的限制。实验室小鼠可能作为一种替代方案，当面临能量短缺时，它们会进入代谢减退和体温过低的状态，类似于冬眠时观察到的麻木状态。值得注意的是，与每天冬眠的物种相比，长时间的热量限制（CR）会导致小鼠连续的日常麻木模式。在这里，我们检查了雄性 C57BL/6 小鼠海马中的神经炎症反应，这些小鼠每天接受 30% CR 诱导的连续麻木状态，持续 4 周。在每天的麻木发作期间，CR 小鼠表现出 TNF-α mRNA 表达的短暂增加，并在唤醒时恢复正常。同时，海马 CA1 区的小胶质细胞表现出持续的形态变化，其特征是细胞分支减少、细胞复杂性降低和形状改变。重要的是，这些形态变化并不伴有明显的星形胶质细胞增生或氧化应激迹象，通常与有害的神经炎症有关。总的来说，小鼠大脑对 CR 诱导的麻木状态的炎症反应的适应性与在冬眠者中的观察结果相似，突出了其对于研究麻木期间大脑恢复机制的价值。这些见解可能为人类中风和神经退行性疾病的新型治疗干预措施铺平道路。