Czerniczyniec A, La Padula P, Bustamante J, Karadayian A G, Lores-Arnaiz S, Costa L E
Instituto de Bioquímica y Medicina Molecular (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Brain Res. 2015 Feb 19;1598:66-75. doi: 10.1016/j.brainres.2014.12.018. Epub 2014 Dec 16.
Taking into account the importance of aerobic metabolism in brain, the aim of the present work was to evaluate mitochondrial function in cerebral cortex and hippocampus in a model of sustained hypobaric hypoxia (5000 m simulated altitude) during a short (1 mo) and a long (7 mo) term period, in order to precise the mechanisms involved in hypoxia acclimatization. Hippocampal mitochondria from rats exposed to short-term hypobaric hypoxia showed lower respiratory rates than controls in both states 4 (45%) and 3 (41%), and increased NO production (1.3 fold) as well as eNOS and nNOS expression associated to mitochondrial membranes, whereas mitochondrial membrane potential decreased (7%). No significant changes were observed in cortical mitochondria after 1 mo hypobaric hypoxia in any of the mitochondrial functionality parameters evaluated. After 7 mo hypobaric hypoxia, oxygen consumption was unchanged as compared with control animals both in hippocampal and cortical mitochondria, but mitochondrial membrane potential decreased by 16% and 8% in hippocampus and cortex respectively. Also, long-term hypobaric hypoxia induced an increase in hippocampal NO production (0.7 fold) and in eNOS expression. A clear tendency to decrease in H2O2 production was observed in both tissues. Results suggest that after exposure to hypobaric hypoxia, hippocampal mitochondria display different responses than cortical mitochondria. Also, the mechanisms responsible for acclimatization to hypoxia would be time-dependent, according to the physiological functions of the brain studied areas. Nitric oxide metabolism and membrane potential changes would be involved as self-protective mechanisms in high altitude environment.
考虑到有氧代谢在大脑中的重要性，本研究旨在评估在短期（1个月）和长期（7个月）持续低压缺氧（模拟海拔5000米）模型中大脑皮层和海马体的线粒体功能，以明确缺氧适应所涉及的机制。暴露于短期低压缺氧的大鼠海马体线粒体在状态4（降低45%）和状态3（降低41%）时的呼吸速率均低于对照组，一氧化氮生成增加（1.3倍），且与线粒体膜相关的内皮型一氧化氮合酶（eNOS）和神经元型一氧化氮合酶（nNOS）表达增加，而线粒体膜电位降低（7%）。在评估的任何线粒体功能参数方面，低压缺氧1个月后，皮层线粒体未观察到显著变化。低压缺氧7个月后，与对照动物相比，海马体和皮层线粒体的氧消耗均未改变，但海马体和皮层的线粒体膜电位分别降低了16%和8%。此外，长期低压缺氧导致海马体一氧化氮生成增加（0.7倍）和eNOS表达增加。在两个组织中均观察到过氧化氢生成有明显下降趋势。结果表明，暴露于低压缺氧后，海马体线粒体与皮层线粒体表现出不同的反应。此外，根据所研究脑区的生理功能，缺氧适应机制可能具有时间依赖性。一氧化氮代谢和膜电位变化可能作为高海拔环境中的自我保护机制参与其中。
