Stage-dependent effects of intermittent hypoxia influence the outcome of hippocampal adult neurogenesis.

Stage-dependent effects of intermittent hypoxia influence the outcome of hippocampal adult neurogenesis.
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DOI:
10.1038/s41598-021-85357-5
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发表时间:
2021-03-16
期刊:
影响因子:
4.6
通讯作者:
Garcia Iii AJ
Garcia Iii AJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Khuu MA;Nallamothu T;Castro-Rivera CI;Arias-Cavieres A;Szujewski CC;Garcia Iii AJ

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据估计,全世界有超过10亿成年人患有睡眠呼吸暂停,这是一种对大脑健康产生广泛影响的疾病。睡眠呼吸暂停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危险因素。啮齿动物暴露于间歇性缺氧(IH),睡眠呼吸暂停的标志,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创建一个促氧化剂的条件下,减少Tbr 2+神经祖细胞池的早期过程中,同时也抑制终末分化的成年出生的神经元在晚期成人神经发生。我们进一步表明,IH依赖性细胞自主缺氧诱导因子1-α(HIF 1a)信号在早期神经祖细胞中被激活,并在IH终止后增强成人出生神经元的生成。我们的研究结果表明,在氧稳态的振荡,如睡眠呼吸暂停中发现的,有复杂的阶段依赖性海马成年神经发生的影响。
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.
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