Neurobiology of the Naked Mole-Rat

裸鼹鼠的神经生物学

• 批准号: 1655494
• 负责人: Thomas Park
• 金额: $ 100万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1655494&HistoricalAwards=false
• 关键词: Neurobiology; Naked; Mole; Rat

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.

裸鼹鼠是不寻常的，因为他们结合了联合收割机的地下生活方式和生活在大的殖民地。由于许多动物呼吸着同样的污浊空气，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。他们的大脑对缺氧的影响有抵抗力。该项目的目标是确定使裸鼹鼠耐受的潜在生理和遗传因素。这对于了解动物为适应环境而改变的多种方式非常重要。这对于确定缺氧生存的新方法也很重要，缺氧发生在心脏病发作的人的大脑中。当心脏衰竭时，血液不能再将氧气输送到大脑。该项目还包括培训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，向人们介绍裸鼹鼠有趣的生物学特性。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性的？这将使用生理学、生物化学和遗传学技术进行研究。生理学方法将包括记录脑电图（EEG）和量化暴露于缺氧的动物中与无氧代谢相关的代谢物。该项目还将使用海马脑切片来测量基本突触现象中与年龄相关的变化，包括长时程增强和长时程抑制。质谱法将用于确定缺氧诱导的程序性细胞死亡途径上磷酸化位点的功能性（磷酸化动力学）。最后，CRISPR/cas9技术将用于产生细胞系和突变小鼠，这些小鼠在缺氧诱导的程序性细胞死亡途径中携带裸鼹鼠突变。这些结果有望揭示建立大脑保护免受缺氧的新方法。

项目成果

Pharmacological targeting of the mammalian clock reveals a novel analgesic for osteoarthritis-induced pain.

• DOI: 10.1016/j.gene.2018.02.048
• 发表时间: 2018-05-20
• 期刊: Gene
• 影响因子: 3.5
• 作者: Das V;Kc R;Li X;Varma D;Qiu S;Kroin JS;Forsyth CB;Keshavarzian A;van Wijnen AJ;Park TJ;Stein GS;O-Sullivan I;Burris TP;Im HJ
• 通讯作者: Im HJ

Independent evolution of pain insensitivity in African mole-rats: origins and mechanisms

非洲鼹鼠疼痛不敏感的独立进化：起源和机制

• DOI: 10.1007/s00359-020-01414-w
• 发表时间: 2020
• 期刊: Journal of Comparative Physiology A
• 作者: Smith, Ewan St.;Park, Thomas J.;Lewin, Gary R.
• 通讯作者: Lewin, Gary R.

Epigenetic aging of the demographically non-aging naked mole-rat.

• DOI: 10.1038/s41467-022-27959-9
• 发表时间: 2022-01-17
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Kerepesi C;Meer MV;Ablaeva J;Amoroso VG;Lee SG;Zhang B;Gerashchenko MV;Trapp A;Yim SH;Lu AT;Levine ME;Seluanov A;Horvath S;Park TJ;Gorbunova V;Gladyshev VN
• 通讯作者: Gladyshev VN

Rapid molecular evolution of pain insensitivity in multiple African rodents

• DOI: 10.1126/science.aau0236
• 发表时间: 2019-05-31
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Eigenbrod, Ole;Debus, Karlien Y.;Lewin, Gary R.
• 通讯作者: Lewin, Gary R.

Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats.

• DOI: 10.1016/j.cub.2020.08.035
• 发表时间: 2020-11-16
• 期刊: Current biology : CB
• 作者: Pyott SJ;van Tuinen M;Screven LA;Schrode KM;Bai JP;Barone CM;Price SD;Lysakowski A;Sanderford M;Kumar S;Santos-Sacchi J;Lauer AM;Park TJ
• 通讯作者: Park TJ