Matching ATP supply and demand is key to neuronal hypoxia-tolerance and failure to achieve this balance leads to excitotoxic cell death in most adult mammalian brains. Ion pumping is the most energy-demanding process in the brain and some hypoxia-tolerant vertebrates coordinately down-regulate ion movement across neuronal membranes to reduce the workload of energy-expensive ion pumps, and particularly the Na⁺/K⁺-ATPase. Naked mole-rats are among the most hypoxia-tolerant mammals and achieve a hypometabolic state while maintaining brain [ATP] during severe hypoxia; however, whether ionic homeostasis is plastic in naked mole-rat brain is unknown. To examine this question, we exposed animals to 4 h of normoxia or moderate or severe hypoxia (11 or 3% O₂, respectively) and measured changes in brain Na⁺/K⁺-ATPase activity. We found that 1) whole body metabolic rate decreased ∼ 25 and 75% in moderate and severe hypoxia, respectively, 2) Na⁺/K⁺-ATPase activity decreased ∼ 50% in forebrain but increased 2-fold in cerebellum and was unchanged in brainstem. These results indicate that naked mole-rats acutely modulate brain energy demand in a region-specific manner to prioritize energy usage by the cerebellum. This may support exploration, navigation, and escape behaviours, while also enabling ATP savings when encountering hypoxia in nature.

匹配 ATP 供需是神经元缺氧耐受性的关键，而未能实现这种平衡会导致大多数成年哺乳动物大脑中的兴奋性毒性细胞死亡。离子泵是大脑中最需要能量的过程，一些耐缺氧的脊椎动物协调下调离子在神经元膜上的运动，以减少高能量离子泵的工作量，特别是 Na ⁺ /K ⁺ -ATP 酶。裸鼹鼠是最耐缺氧的哺乳动物之一，在严重缺氧期间保持大脑 [ATP] 的同时达到低代谢状态；然而，裸鼹鼠大脑中的离子稳态是否可塑性尚不清楚。为了检验这个问题，我们将动物暴露于 4 小时的常氧或中度或重度缺氧（11 或 3% O ₂, 分别) 和测量脑 Na ⁺ /K ⁺ -ATPase 活性的变化。我们发现 1) 中度和重度缺氧时全身代谢率分别下降 25% 和 75%，2) Na ⁺ /K ⁺ -ATP 酶活性在前脑下降 50%，但在小脑中增加 2 倍，在脑干。这些结果表明，裸鼹鼠以特定区域的方式敏锐地调节大脑能量需求，以优先考虑小脑的能量使用。这可能支持探索、导航和逃生行为，同时在自然界中遇到缺氧时也能节省 ATP。