Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario, Canada.
Acta Physiol (Oxf). 2023 May;238(1):e13963. doi: 10.1111/apha.13963. Epub 2023 Mar 31.
Extreme environments are powerful drivers of physiological adaptation. Naked mole-rats offer an informative example of this relationship as they putatively encounter intermittent hypoxia and hypercapnia in their subterranean habitat. This has presumably driven the evolution of a suite of cellular and physiological adaptations that enable life in these conditions. Recently, my laboratory and others have begun to examine physiological responses to environmental hypoxia and hypercapnia in naked mole-rats, and the underlying cellular and molecular mechanisms that differentiate the responses of this species from those of other small mammals. Prominent among these adaptations are a robust hypoxic metabolic response and blunted ventilatory responses to hypoxia and hypercapnia. These responses are mediated in part by modifications to the central nervous system signaling pathways that sense and communicate changes in environmental gas levels and initiate and maintain downstream physiological responses. For example, naked mole-rats retain the signaling architecture necessary for "normal" ventilatory responses to hypoxia and hypercapnia; however, the underlying signaling pathways are muted, resulting in reduced, or even the absence of, sensitivity to otherwise powerful environmental stimuli. Herein, I discuss what we have learned about the manifestation and control of ventilatory and metabolic responses to hypoxia and hypercapnia in naked mole-rats. I also highlight areas where additional work is warranted and consider the implications of what we have learned for the ecophysiology of a species that thrives in conditions that are deleterious or lethal to most adult mammals.
极端环境是生理适应的强大驱动力。裸鼹鼠为这种关系提供了一个有意义的例子，因为它们在地下栖息地可能会间歇性地缺氧和高碳酸血症。这可能促使它们进化出了一系列细胞和生理适应机制，使它们能够在这些条件下生存。最近，我的实验室和其他实验室开始研究裸鼹鼠对环境缺氧和高碳酸血症的生理反应，以及导致该物种对缺氧和高碳酸血症的反应与其他小型哺乳动物不同的潜在细胞和分子机制。其中突出的适应是对缺氧代谢反应的强大反应和对缺氧和高碳酸血症的通气反应减弱。这些反应部分是由中枢神经系统信号通路的改变介导的，这些信号通路感知和传达环境气体水平的变化，并启动和维持下游的生理反应。例如，裸鼹鼠保留了对缺氧和高碳酸血症“正常”通气反应所需的信号结构；然而，潜在的信号通路被抑制，导致对其他强大环境刺激的敏感性降低，甚至缺失。在此，我讨论了我们对裸鼹鼠对缺氧和高碳酸血症的通气和代谢反应的表现和控制所了解的情况。我还强调了需要进一步研究的领域，并考虑了我们所学到的对在对大多数成年哺乳动物有害或致命的条件下茁壮成长的物种的生态生理学的影响。
