Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Capital Medical University, Beijing, China.
CNS Neurosci Ther. 2022 Aug;28(8):1183-1194. doi: 10.1111/cns.13849. Epub 2022 May 18.
Acute high-altitude hypoxia exposure causes multiple adverse neurological consequences. However, the exact mechanisms are still unclear, and there is no targeted treatment with few side effects. Excessive cerebral formaldehyde (FA) impairs numerous functions, and can be eliminated by nano-packed coenzyme Q10 (CoQ10).
In this study, we aimed to investigate whether cerebral FA was accumulated after hypobaric hypoxia exposure, and further explored the preventative effect of CoQ10 through FA elimination.
Accumulated cerebral FA was found in C57BL/6 mice after acute high-altitude hypoxia exposure, which resulted in FA metabolic disturbance with the elevation of semicarbazide-sensitive amine oxidase, and declination of aldehyde dehydrogenase-2. Excessive FA was also found to induce neuronal ferroptosis in vivo. Excitingly, administration with CoQ10 for 3 days before acute hypobaric hypoxia reduced cerebral FA accumulation, alleviated subsequent neuronal ferroptosis, and preserved neurological functions.
Cerebral FA accumulation mediates neurological deficits under acute hypobaric hypoxia, and CoQ10 supplementation may be a promising preventative strategy for visitors and sojourners at plateau.
急性高空缺氧暴露会导致多种不良的神经后果。然而，确切的机制尚不清楚，而且针对这种情况的治疗方法很少，副作用也很少。过多的脑甲醛（FA）会损害多种功能，而纳米包装的辅酶 Q10（CoQ10）可以消除它。
在这项研究中，我们旨在研究急性低压缺氧暴露后是否会积累脑 FA，以及通过消除 FA 进一步探索 CoQ10 的预防作用。
急性高空缺氧暴露后，C57BL/6 小鼠的脑中发现了累积的 FA，导致 FA 代谢紊乱，半卡巴嗪敏感胺氧化酶升高，醛脱氢酶-2 下降。过量的 FA 也被发现会在体内诱导神经元铁死亡。令人兴奋的是，在急性低压缺氧前用 CoQ10 治疗 3 天可以减少脑 FA 的积累，减轻随后的神经元铁死亡，并保护神经功能。
脑 FA 积累介导了急性低压缺氧下的神经功能缺损，而 CoQ10 的补充可能是高原游客和逗留者的一种有前途的预防策略。
