Neurobiology of the Naked Mole-Rat

裸鼹鼠是不寻常的，因为它们结合了地下的生活方式和大群体的生活方式。由于许多动物呼吸同样的污浊空气，氧气供应变得很低。与此相一致的是，裸鼹鼠对缺氧具有极强的耐受性。他们的大脑能抵抗缺氧的影响。该项目的目标是确定裸鼹鼠耐受性的潜在生理和遗传因素。这对于理解动物为适应环境而改变的各种方式非常重要。这对于确定缺氧生存的新方法也很重要，这种情况发生在患有心脏病的人的大脑中。当心脏衰竭时，血液就不能再向大脑输送氧气。该项目还包括培养研究生和本科生成为科学家。项目工作人员将在一个免费的城市动物园与公众互动，向人们介绍裸鼹鼠的有趣生物学。要研究的问题是，裸鼹鼠是如何实现大脑对缺氧的极端耐受的？这将使用生理、生化和遗传技术进行研究。生理学方法将包括记录脑电图（EEG）和量化与缺氧动物无氧代谢相关的代谢物。该项目还将使用海马体大脑切片来测量与年龄相关的基本突触现象的变化，包括长期增强和长期抑郁。质谱法将用于确定缺氧诱导的程序性细胞死亡途径中磷酸化位点的功能（磷酸化动力学）。最后，CRISPR/cas9技术将用于生产在缺氧诱导的程序性细胞死亡途径中携带裸鼹鼠突变的细胞系和突变小鼠。研究结果有望揭示建立大脑缺氧保护机制的新方法。

Naked mole-rats are unusual because they combine a subterranean lifestyle with living in large colonies. With many animals breathing the same stale air, oxygen supplies become low. Consistent with this, naked mole-rats are extremely tolerant to oxygen deprivation. Their brain is resistant to the effects of oxygen deprivation. The goal of the project is to identify the underlying physiological and genetic factors that give the naked mole-rat its tolerance. This will be important for understanding the diverse ways that animals can change to fit their environment. It will also be important for identifying new ways of surviving oxygen deprivation, which happens in the brain of a human who suffers a heart attack. Blood can no longer carry oxygen to the brain when the heart fails. The project also includes training graduate and undergraduate students to be scientists. Project staff will interact with the public at a free city zoo to inform people about the interesting biology of the naked mole-rat.The problem to be studied is, how do naked mole-rats achieve extreme brain tolerance to oxygen deprivation? This will be studied using physiological, biochemical, and genetic techniques. Physiological approaches will include recording electroencephalograms (EEG) and quantifying metabolites related to anaerobic metabolism in animals exposed to hypoxia. The project will also use hippocampal brain slices to measure age-related changes in basic synaptic phenomena including long-term potentiation and long-term depression. Mass spectrometry will be used to determine the functionality (phosphorylation dynamics) of phosphorylation sites on hypoxia-induced programed cell death pathways. Finally, CRISPR/cas9 techniques will be used to produce both cell lines and mutant mice that carry naked mole-rat mutations in hypoxia-induced programed cell death pathways. The results are expected to reveal new ways of establishing brain protection from oxygen deprivation.