Institute for Integrative Physiology, Section of Emergency Medicine, The University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA.
Committee On Neurobiology, The University of Chicago, Chicago, IL, 60307, USA.
Sci Rep. 2021 Mar 16;11(1):6005. doi: 10.1038/s41598-021-85357-5.
Over one billion adults worldwide are estimated to suffer from sleep apnea, a condition with wide-reaching effects on brain health. Sleep apnea causes cognitive decline and is a risk factor for neurodegenerative conditions such as Alzheimer's disease. Rodents exposed to intermittent hypoxia (IH), a hallmark of sleep apnea, exhibit spatial memory deficits associated with impaired hippocampal neurophysiology and dysregulated adult neurogenesis. We demonstrate that IH creates a pro-oxidant condition that reduces the Tbr2 neural progenitor pool early in the process, while also suppressing terminal differentiation of adult born neurons during late adult neurogenesis. We further show that IH-dependent cell-autonomous hypoxia inducible factor 1-alpha (HIF1a) signaling is activated in early neuroprogenitors and enhances the generation of adult born neurons upon termination of IH. Our findings indicate that oscillations in oxygen homeostasis, such as those found in sleep apnea, have complex stage-dependent influence over hippocampal adult neurogenesis.
据估计，全球有超过 10 亿成年人患有睡眠呼吸暂停症，这种病症对大脑健康有广泛的影响。睡眠呼吸暂停症会导致认知能力下降，是阿尔茨海默病等神经退行性疾病的一个风险因素。暴露于间歇性低氧（IH）的啮齿动物，这是睡眠呼吸暂停的一个标志，表现出与海马神经生理学受损和成年神经发生失调相关的空间记忆缺陷。我们证明 IH 会造成一种促氧化剂条件，在早期过程中减少 Tbr2 神经祖细胞池，同时在成年神经发生后期抑制成年新生神经元的终末分化。我们还进一步表明，IH 依赖性细胞自主缺氧诱导因子 1-α（HIF1a）信号在早期神经祖细胞中被激活，并在 IH 终止时增强成年新生神经元的产生。我们的研究结果表明，类似于睡眠呼吸暂停中发现的那样，氧气动态平衡的波动对海马体成年神经发生具有复杂的、与阶段相关的影响。
