Radhakrishnan Jeejabai, Baetiong Alvin, Gazmuri Raúl J
Resuscitation Institute, Rosalind Franklin University of Medicine and Science, 3333, Green Bay Rd, North Chicago, Illinois 60064, USA; Department of Clinical Sciences, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
Resuscitation Institute, Rosalind Franklin University of Medicine and Science, 3333, Green Bay Rd, North Chicago, Illinois 60064, USA; Department of Clinical Sciences, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
Physiol Behav. 2020 May 15;219:112828. doi: 10.1016/j.physbeh.2020.112828. Epub 2020 Feb 13.
We recently reported that constitutive ablation of cyclophilin-D (Cyp-D) in mice reduces oxygen consumption (VO) while paradoxically increasing exercise endurance, thereby demonstrating increased O utilization efficiency. This response was associated with augmented glucose uptake and glucose utilization, in part mediated through adenosine monophosphate-activated kinase signaling. We now hypothesized that Cyp-D knock-out (KO) mice might also exhibit improved cognitive-behavioral performance and that these favorable adaptive responses may persist under hypoxic conditions. We therefore assessed under normoxic (20.9% O, simulating ground O levels) and hypoxic (8% O, simulating 7600 m altitude O levels) conditions exercise capacity and cognitive-behavioral performance. We used a treadmill test to assess exercise capacity, a pole-test to assess agility, an elevated-plus-maze test to assess anti-anxiety, and a passive avoidance test to assess learning and memory retention. Compared to wild type, Cyp-D KO mice showed comparable treadmill work under normoxia (48 ± 12 vs 47 ± 9 Joules) but increased treadmill work (12 ± 1 vs 8 ± 1 Joules; p = 0.02) under hypoxia. Cyp-D KO mice displayed increased pole-descending time (17 ± 3 vs 8 ± 2 s; p ≤ 0.05) under normoxia but shorter pole-descending time (21 ± 3 vs 37 ± 4 s; p ≤ 0.01) under hypoxia. In addition, the Cyp-D KO mice demonstrated increased elevated plus-maze open arm time (91 ± 31 vs 23 ± 12 s; p ≤ 0.05) under hypoxia and increased latency to enter dark chamber (261 ± 23 vs 185 ± 42 s; p ≤ 0.05) under normoxia. Thus, our experiments showed that under normoxia Cyp-D KO mice displayed anti-anxiety behavior and improved learning and memory retention. Under hypoxia, Cyp-D KO mice displayed increased exercise capacity, increased agility, and increased anti-anxiety consistent with our previously reported findings of increased O utilization efficiency. Identifying interventions to elicit these effects could be beneficial in a myriad of physiological and clinical conditions in which increasing O utilization efficiency would be advantageous.
我们最近报道，在小鼠中组成型敲除亲环蛋白-D（Cyp-D）可降低耗氧量（VO），同时反常地提高运动耐力，从而证明氧利用效率提高。这种反应与葡萄糖摄取和葡萄糖利用增加有关，部分是通过腺苷单磷酸激活的蛋白激酶信号传导介导的。我们现在推测，Cyp-D基因敲除（KO）小鼠可能也表现出改善的认知行为表现，并且这些有利的适应性反应在低氧条件下可能持续存在。因此，我们在常氧（20.9% O，模拟地面氧水平）和低氧（8% O，模拟海拔7600米的氧水平）条件下评估了运动能力和认知行为表现。我们使用跑步机测试来评估运动能力，杆测试来评估敏捷性，高架十字迷宫测试来评估抗焦虑能力，以及被动回避测试来评估学习和记忆保持能力。与野生型相比，Cyp-D KO小鼠在常氧下跑步机工作表现相当（48±12对47±9焦耳），但在低氧下跑步机工作增加（12±1对8±1焦耳；p = 0.02）。Cyp-D KO小鼠在常氧下杆下降时间增加（17±3对8±2秒；p≤0.05），但在低氧下杆下降时间缩短（21±3对37±4秒；p≤0.01）。此外，Cyp-D KO小鼠在低氧下高架十字迷宫开放臂时间增加（91±31对23±12秒；p≤0.05），在常氧下进入暗室的潜伏期增加（261±23对185±42秒；p≤0.05）。因此，我们的实验表明，在常氧下Cyp-D KO小鼠表现出抗焦虑行为以及改善的学习和记忆保持能力。在低氧条件下，Cyp-D KO小鼠表现出运动能力增加、敏捷性增加以及抗焦虑能力增加，这与我们之前报道的氧利用效率增加的发现一致。确定引发这些效应的干预措施可能对众多生理和临床状况有益，在这些状况中提高氧利用效率将是有利的。
