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实验性“时差”抑制成年神经发生并导致雌性仓鼠长期认知缺陷。

Experimental 'jet lag' inhibits adult neurogenesis and produces long-term cognitive deficits in female hamsters.

机构信息

Department of Psychology, University of California, Berkeley, California, United States of America.

出版信息

PLoS One. 2010 Dec 1;5(12):e15267. doi: 10.1371/journal.pone.0015267.

Abstract

BACKGROUND

Circadian disruptions through frequent transmeridian travel, rotating shift work, and poor sleep hygiene are associated with an array of physical and mental health maladies, including marked deficits in human cognitive function. Despite anecdotal and correlational reports suggesting a negative impact of circadian disruptions on brain function, this possibility has not been experimentally examined.

METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we investigated whether experimental 'jet lag' (i.e., phase advances of the light:dark cycle) negatively impacts learning and memory and whether any deficits observed are associated with reductions in hippocampal cell proliferation and neurogenesis. Because insults to circadian timing alter circulating glucocorticoid and sex steroid concentrations, both of which influence neurogenesis and learning/memory, we assessed the contribution of these endocrine factors to any observed alterations. Circadian disruption resulted in pronounced deficits in learning and memory paralleled by marked reductions in hippocampal cell proliferation and neurogenesis. Significantly, deficits in hippocampal-dependent learning and memory were not only seen during the period of the circadian disruption, but also persisted well after the cessation of jet lag, suggesting long-lasting negative consequences on brain function.

CONCLUSIONS/SIGNIFICANCE: Together, these findings support the view that circadian disruptions suppress hippocampal neurogenesis via a glucocorticoid-independent mechanism, imposing pronounced and persistent impairments on learning and memory.

摘要

背景

通过频繁的跨时区旅行、轮班工作和不良的睡眠卫生习惯,昼夜节律紊乱与一系列身心健康问题有关,包括人类认知功能明显下降。尽管有传闻和相关报道表明昼夜节律紊乱对大脑功能有负面影响,但这一可能性尚未通过实验进行检验。

方法/主要发现:在本研究中,我们研究了实验性“时差”(即光暗周期的相位提前)是否会对学习和记忆产生负面影响,以及是否观察到任何缺陷与海马体细胞增殖和神经发生减少有关。由于昼夜节律计时的干扰会改变循环中的糖皮质激素和性激素浓度,而这两者都会影响神经发生和学习/记忆,我们评估了这些内分泌因素对任何观察到的变化的贡献。昼夜节律紊乱导致学习和记忆明显受损,同时伴有海马体细胞增殖和神经发生明显减少。值得注意的是,海马体依赖性学习和记忆的缺陷不仅在昼夜节律紊乱期间出现,而且在时差结束后仍持续存在,表明对大脑功能产生持久的负面影响。

结论/意义:总之,这些发现支持了这样一种观点,即昼夜节律紊乱通过一种非糖皮质激素依赖的机制抑制海马体神经发生,对学习和记忆造成明显和持久的损害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01f1/2995744/cf4dfdef352c/pone.0015267.g001.jpg

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