40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice.

IF 13 1区 生物学 Q1 CELL BIOLOGY Cell Discovery Pub Date : 2024-08-06 DOI:10.1038/s41421-024-00701-z
Xiaoting Sun, Liliana Dias, Chenlei Peng, Ziyi Zhang, Haoting Ge, Zejun Wang, Jiayi Jin, Manli Jia, Tao Xu, Wei Guo, Wu Zheng, Yan He, Youru Wu, Xiaohong Cai, Paula Agostinho, Jia Qu, Rodrigo A Cunha, Xuzhao Zhou, Ruiliang Bai, Jiang-Fan Chen
{"title":"40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice.","authors":"Xiaoting Sun, Liliana Dias, Chenlei Peng, Ziyi Zhang, Haoting Ge, Zejun Wang, Jiayi Jin, Manli Jia, Tao Xu, Wei Guo, Wu Zheng, Yan He, Youru Wu, Xiaohong Cai, Paula Agostinho, Jia Qu, Rodrigo A Cunha, Xuzhao Zhou, Ruiliang Bai, Jiang-Fan Chen","doi":"10.1038/s41421-024-00701-z","DOIUrl":null,"url":null,"abstract":"<p><p>The glymphatic-lymphatic system is increasingly recognized as fundamental for the homeostasis of the brain milieu since it defines cerebral spinal fluid flow in the brain parenchyma and eliminates metabolic waste. Animal and human studies have uncovered several important physiological factors regulating the glymphatic system including sleep, aquaporin-4, and hemodynamic factors. Yet, our understanding of the modulation of the glymphatic system is limited, which has hindered the development of glymphatic-based treatment for aging and neurodegenerative disorders. Here, we present the evidence from fluorescence tracing, two-photon recording, and dynamic contrast-enhanced magnetic resonance imaging analyses that 40 Hz light flickering enhanced glymphatic influx and efflux independently of anesthesia and sleep, an effect attributed to increased astrocytic aquaporin-4 polarization and enhanced vasomotion. Adenosine-A<sub>2A</sub> receptor (A<sub>2A</sub>R) signaling emerged as the neurochemical underpinning of 40 Hz flickering-induced enhancement of glymphatic flow, based on increased cerebrofluid adenosine levels, the abolishment of enhanced glymphatic flow by pharmacological or genetic inactivation of equilibrative nucleotide transporters-2 or of A<sub>2A</sub>R, and by the physical and functional A<sub>2A</sub>R-aquaporin-4 interaction in astrocytes. These findings establish 40 Hz light flickering as a novel non-invasive strategy of enhanced glymphatic flow, with translational potential to relieve brain disorders.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":null,"pages":null},"PeriodicalIF":13.0000,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300858/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Discovery","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41421-024-00701-z","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The glymphatic-lymphatic system is increasingly recognized as fundamental for the homeostasis of the brain milieu since it defines cerebral spinal fluid flow in the brain parenchyma and eliminates metabolic waste. Animal and human studies have uncovered several important physiological factors regulating the glymphatic system including sleep, aquaporin-4, and hemodynamic factors. Yet, our understanding of the modulation of the glymphatic system is limited, which has hindered the development of glymphatic-based treatment for aging and neurodegenerative disorders. Here, we present the evidence from fluorescence tracing, two-photon recording, and dynamic contrast-enhanced magnetic resonance imaging analyses that 40 Hz light flickering enhanced glymphatic influx and efflux independently of anesthesia and sleep, an effect attributed to increased astrocytic aquaporin-4 polarization and enhanced vasomotion. Adenosine-A2A receptor (A2AR) signaling emerged as the neurochemical underpinning of 40 Hz flickering-induced enhancement of glymphatic flow, based on increased cerebrofluid adenosine levels, the abolishment of enhanced glymphatic flow by pharmacological or genetic inactivation of equilibrative nucleotide transporters-2 or of A2AR, and by the physical and functional A2AR-aquaporin-4 interaction in astrocytes. These findings establish 40 Hz light flickering as a novel non-invasive strategy of enhanced glymphatic flow, with translational potential to relieve brain disorders.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
40赫兹的灯光闪烁可通过腺苷信号促进小鼠的甘液流。
人们日益认识到,甘液-淋巴系统对大脑环境的平衡至关重要,因为它决定了脑实质中脑脊液的流动并清除代谢废物。动物和人体研究发现了调节甘液系统的几个重要生理因素,包括睡眠、水蒸发素-4 和血液动力学因素。然而,我们对甘液系统调控的了解还很有限,这阻碍了基于甘液系统治疗衰老和神经退行性疾病的发展。在这里,我们通过荧光追踪、双光子记录和动态对比增强磁共振成像分析证明,40 Hz 灯光闪烁可增强甘液流入和流出,而不受麻醉和睡眠的影响。腺苷-A2A受体(A2AR)信号传导是40赫兹闪烁诱导的甘油流增强的神经化学基础,其依据是脑血流中腺苷水平的增加、平衡核苷酸转运体-2或A2AR的药物或遗传失活对甘油流增强的抑制,以及星形胶质细胞中A2AR-aquaporin-4在物理和功能上的相互作用。这些研究结果表明,40 Hz 灯光闪烁是一种新型的非侵入性增强甘液流动的策略,具有缓解脑部疾病的转化潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
期刊最新文献
Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys. Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation. Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer. NUMB dysfunction defines a novel mechanism underlying hyperuricemia and gout. A spatiotemporal transcriptomic atlas of mouse placentation.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1