Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.
School of Electronic Information Science and Technology, Nantong University, Nantong, Jiangsu Province, China.
Adv Exp Med Biol. 2021;1269:271-276. doi: 10.1007/978-3-030-48238-1_43.
Hypoxia-inducible factors (HIFs) are transcriptional regulators that mediate in mice for HIF-1 and HIF-2. The objective of this study was to investigate the effect of neuronal deletion of HIF-1 and HIF-2 in hypoxic adaptation by using the neuron-specific knockout (KO) mice. The floxed control and KO mice were used. Hypoxic mice were kept in a hypobaric chamber at a pressure of 300 torr (0.4 ATM, which was equivalent to 8% oxygen under normobaric condition) for 3 weeks. The littermate, normoxic control mice were housed in the same room next to the chamber to match ambient conditions. Body weights were monitored throughout the 3-week course. Cognitive function was measured using a Y-maze test; motor functions were measured using the rotarod test and the grip strength test. The hematocrit increased significantly at the end of 3-week hypoxic exposure in both control and KO mice. In the Y-maze test, the alternation rate (indicative of sustained cognition) trended lower in the KO mice compared to the controls following hypoxia (%, 51.3 ± 13.1, n = 6 vs. 63.2 ± 12.0, n = 8). In the rotarod test, the latency (seconds) in the KO mice was significantly lower compared to the controls (50.4 ± 5.7 vs. 77.1 ± 5.0, n = 3 each before hypoxia and 66.4 ± 3.4, n = 6 vs. 98.1 ± 15.4 after hypoxia, n = 3). The grip strength in the KO mice was similar compared to the control mice before hypoxia, but the strength of KO mice trended higher after hypoxic exposure. Our data suggest that deficiency of neuronal HIF-1 and HIF-2 may result in changes in behavioral performance and other adaptative responses to hypoxia.
缺氧诱导因子（HIFs）是转录调节因子，在小鼠中介导 HIF-1 和 HIF-2。本研究的目的是使用神经元特异性敲除（KO）小鼠研究缺氧适应中神经元 HIF-1 和 HIF-2 的缺失的影响。使用 floxed 对照和 KO 小鼠。将缺氧小鼠置于 300 毫托（0.4 ATM，相当于常压低氧条件下的 8%氧气）的减压室中 3 周。同窝对照、常氧对照小鼠被安置在减压室隔壁的房间中，以匹配环境条件。在整个 3 周的过程中监测体重。使用 Y 迷宫测试测量认知功能；使用转棒测试和握力测试测量运动功能。在 3 周的缺氧暴露结束时，对照和 KO 小鼠的红细胞压积均显著增加。在 Y 迷宫测试中，与对照相比，缺氧后 KO 小鼠的交替率（提示持续认知）呈下降趋势（%，51.3±13.1，n=6 与 63.2±12.0，n=8）。在转棒测试中，与对照相比，KO 小鼠的潜伏期（秒）显著降低（50.4±5.7 与 77.1±5.0，n=3 分别在缺氧前和 66.4±3.4，n=6 与 98.1±15.4，n=3 缺氧后）。在缺氧前，KO 小鼠的握力与对照相似，但缺氧后 KO 小鼠的握力趋势较高。我们的数据表明，神经元 HIF-1 和 HIF-2 的缺乏可能导致行为表现和其他对缺氧的适应性反应的变化。
