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长时间的白天可以增强识别记忆,并增加海马体中的胰岛素样生长因子 2。

Long days enhance recognition memory and increase insulin-like growth factor 2 in the hippocampus.

机构信息

Department of Biomedical Sciences, Marquette University, Milwaukee, WI, 53233, USA.

Departments of Biology & Neuroscience, Johns Hopkins University, Baltimore, MD, 21218, USA.

出版信息

Sci Rep. 2017 Jun 20;7(1):3925. doi: 10.1038/s41598-017-03896-2.

Abstract

Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod. Long days enhanced long-term recognition memory, and this effect was abolished by loss of the photopigment melanopsin. Further, long days markedly altered hippocampal clock function and elevated transcription of Insulin-like Growth Factor2 (Igf2). Up-regulation of Igf2 occurred in tandem with suppression of its transcriptional repressor Wilm's tumor1. Consistent with molecular de-repression of Igf2, IGF2 expression was increased in the hippocampus before and after memory training. Lastly, long days occluded IGF2-induced improvements in recognition memory. Collectively, these results suggest that light changes hippocampal clock function to alter memory, highlighting novel mechanisms that may contribute to the positive effects of light. Furthermore, this study provides insight into how the circadian clock can regulate hippocampus-dependent learning by controlling molecular processes required for memory consolidation.

摘要

光照可以改善人类的认知功能;然而,光照对认知产生积极影响的神经生物学机制仍不清楚。其中一个障碍是,大多数啮齿动物模型采用的光照条件会导致认知缺陷,而不是改善。在这里,我们开发了一种光照可以改善认知功能的小鼠模型,这为光照对认知产生积极影响的机制提供了深入的了解。为了在不消除日常节律的情况下增加光照暴露,我们让小鼠暴露在标准光周期或长日光周期下。长日增加了长期识别记忆,而这种效应在光色素 melanopsin 缺失时被消除。此外,长日显著改变了海马体的时钟功能,并提高了胰岛素样生长因子 2(Igf2)的转录。IGF2 的上调与转录抑制因子 Wilm 肿瘤 1(Wilm's tumor 1,Wt1)的抑制同时发生。与 Igf2 的分子去抑制一致,在记忆训练前后,海马体中的 IGF2 表达增加。最后,长日抑制了 IGF2 诱导的识别记忆改善。总之,这些结果表明,光照改变了海马体的时钟功能以改变记忆,突出了可能有助于光照积极影响的新机制。此外,这项研究提供了关于生物钟如何通过控制记忆巩固所需的分子过程来调节海马体依赖学习的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dea9/5478617/13cbe28c0f7c/41598_2017_3896_Fig1_HTML.jpg

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