Constitutive cyclophilin-D ablation in mice increases exercise and cognitive-behavioral performance under normoxic and hypoxic conditions.
Constitutive cyclophilin-D ablation in mice increases exercise and cognitive-behavioral performance under normoxic and hypoxic conditions.
复制标题
小鼠体内亲环蛋白-D 的组成型消融可增加常氧和缺氧条件下的运动和认知行为表现。
DOI：
10.1016/j.physbeh.2020.112828
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发表时间：
2020
影响因子：
2.9
通讯作者：
Gazmuri,RaúlJ
中科院分区：
文献类型：
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作者：
Radhakrishnan,Jeejabai;Baetiong,Alvin;Gazmuri,RaúlJ
我们最近报道，在小鼠体内，结构性消融亲环素-D(Cyp-D)可以减少氧耗(VO2)，同时反常地增加运动耐力，从而证明提高了O2的利用效率。这种反应与葡萄糖摄取和葡萄糖利用的增加有关，部分是通过一磷酸腺苷激活的激酶信号来调节的。我们现在假设，Cyp-D基因敲除(KO)小鼠也可能表现出改善的认知行为表现，并且这些有利的适应性反应可能在低氧条件下持续存在。因此，我们评估了常氧(20.9%O2，模拟地面O2水平)和低氧(8%O2，模拟7600米海拔O2水平)条件下的运动能力和认知行为表现。我们用跑步机测试来评估运动能力，用杆子测试来评估灵活性，用高架加迷宫测试来评估抗焦虑能力，用被动回避测试来评估学习和记忆保持。与野生型相比，Cyp-D KO小鼠在常氧下的跑台运动(48±12比47±9焦耳)与野生型相当，但在低氧条件下跑台运动(12±1比8±1焦耳；p=0.02)增加。常氧条件下，CYP-D KO小鼠降极时间延长(17±3vs8±2比S；p≤0.0 5)，缺氧时降极时间缩短(21±3vs37±4比S；p≤0.0 1)。此外，缺氧条件下，Cyp-D KO小鼠打开正迷宫的时间延长(91±31vs23±12对S；p≤0.05)，进入暗室的潜伏期延长(261±23对185±42对S；p≤：0.05)。因此，我们的实验表明，在常氧条件下，Cyp-D KO小鼠表现出抗焦虑行为，并改善了学习和记忆保持。在低氧条件下，Cyp-D KO小鼠表现出更强的运动能力、更高的灵活性和更强的抗焦虑能力，这与我们之前报道的氧气利用效率提高的发现一致。在各种生理和临床情况下，确定干预措施以产生这些影响可能是有益的，在这些情况下，提高氧气利用率将是有利的。
We recently reported that constitutive ablation of cyclophilin-D (Cyp-D) in mice reduces oxygen consumption (VO2) while paradoxically increasing exercise endurance, thereby demonstrating increased O2utilization 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% O2, simulating ground O2levels) and hypoxic (8% O2, simulating 7600 m altitude O2levels) 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 ± 12vs47 ± 9 Joules) but increased treadmill work (12 ± 1vs8 ± 1 Joules;p= 0.02) under hypoxia. Cyp-D KO mice displayed increased pole-descending time (17 ± 3vs8 ± 2 s;p≤ 0.05) under normoxia but shorter pole-descending time (21 ± 3vs37 ± 4 s;p≤ 0.01) under hypoxia. In addition, the Cyp-D KO mice demonstrated increased elevated plus-maze open arm time (91 ± 31vs23 ± 12 s;p≤ 0.05) under hypoxia and increased latency to enter dark chamber (261 ± 23vs185 ± 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 O2utilization efficiency. Identifying interventions to elicit these effects could be beneficial in a myriad of physiological and clinical conditions in which increasing O2utilization efficiency would be advantageous.