Regulation of headache response and transcriptomic network by the trigeminal ganglion clock

昼夜节律 三叉神经节 每2 每1 生物钟 生物 神经科学 时钟 丛集性头痛 医学 内科学 偏头痛 感觉系统
作者
Chorong Han,Ji Ye Lim,Nobuya Koike,Sun Young Kim,Kaori Ono,Celia K. Tran,Elizaveta Mangutov,Eunju Kim,Yanping Zhang,Lingyong Li,Amynah Pradhan,Kazuhiro Yagita,Zheng Chen,Seung‐Hee Yoo,Mark J. Burish
出处
期刊:Headache [Wiley]
卷期号:64 (2): 195-210
标识
DOI:10.1111/head.14670
摘要

Abstract Objective To characterize the circadian features of the trigeminal ganglion in a mouse model of headache. Background Several headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood. Methods We examined trigeminal ganglion ex vivo and single‐cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry. Circadian behavior and transcriptomics were investigated using a novel combination of trigeminovascular and circadian models: a nitroglycerin mouse headache model with mechanical thresholds measured every 6 h, and trigeminal ganglion RNA sequencing measured every 4 h for 24 h. Finally, we performed pharmacogenomic analysis of gene targets for migraine, cluster headache, and trigeminal neuralgia treatments as well as trigeminal ganglion neuropeptides; this information was cross‐referenced with our cycling genes from RNA sequencing data to identify potential targets for chronotherapy. Results The trigeminal ganglion demonstrates strong circadian rhythms in both ex vivo and single‐cell cultures, with core circadian proteins found in both neuronal and non‐neuronal cells. Using our novel behavioral model, we showed that nitroglycerin‐treated mice display circadian rhythms of pain sensitivity which were abolished in arrhythmic Per1 / 2 double knockout mice. Furthermore, RNA‐sequencing analysis of the trigeminal ganglion revealed 466 genes that displayed circadian oscillations in the control group, including core clock genes and clock‐regulated pain neurotransmitters. In the nitroglycerin group, we observed a profound circadian reprogramming of gene expression, as 331 of circadian genes in the control group lost rhythm and another 584 genes gained rhythm. Finally, pharmacogenetics analysis identified 10 genes in our trigeminal ganglion circadian transcriptome that encode target proteins of current medications used to treat migraine, cluster headache, or trigeminal neuralgia. Conclusion Our study unveiled robust circadian rhythms in the trigeminal ganglion at the behavioral, transcriptomic, and pharmacogenetic levels. These results support a fundamental role of the clock in pain pathophysiology. Plain Language Summary Several headache diseases, such as migraine and cluster headache, have headaches that occur at the same time each day. We learned that the trigeminal ganglion, an important pain structure in several headache diseases, has a 24‐hour cycle that might be related to this daily cycle of headaches. Our genetic analysis suggests that some medications may be more effective in treating migraine and cluster headache when taken at specific times of the day.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
喜悦的如雪完成签到,获得积分10
刚刚
左手树完成签到,获得积分10
1秒前
平淡雪枫发布了新的文献求助10
1秒前
xmmm完成签到,获得积分10
1秒前
liu应助烂漫忆山采纳,获得30
1秒前
大1完成签到,获得积分10
1秒前
uniphoton完成签到,获得积分10
3秒前
wen发布了新的文献求助30
3秒前
linnan发布了新的文献求助10
3秒前
乐乐应助冬天好大的雨采纳,获得10
3秒前
4秒前
Kerry完成签到,获得积分10
4秒前
乐乐应助YI采纳,获得10
4秒前
4秒前
博古书生完成签到,获得积分10
5秒前
Linda发布了新的文献求助30
5秒前
5秒前
洪山老狗发布了新的文献求助10
5秒前
阿拉波波完成签到,获得积分10
6秒前
6秒前
BOSS徐发布了新的文献求助10
6秒前
7秒前
7秒前
8秒前
Zhangzj3发布了新的文献求助10
10秒前
非也的非也完成签到,获得积分10
10秒前
Lore完成签到 ,获得积分10
10秒前
goodesBright应助行走的车采纳,获得10
11秒前
奥利奥发布了新的文献求助10
12秒前
消消乐发布了新的文献求助10
12秒前
秃驴完成签到,获得积分10
12秒前
14秒前
14秒前
showitt完成签到,获得积分10
15秒前
灵巧的翠风完成签到 ,获得积分10
15秒前
忆枫完成签到,获得积分10
16秒前
16秒前
17秒前
17秒前
缓慢手机完成签到,获得积分10
17秒前
高分求助中
Sustainability in ’Tides Chemistry 2000
The ACS Guide to Scholarly Communication 2000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Pharmacogenomics: Applications to Patient Care, Third Edition 800
Gerard de Lairesse : an artist between stage and studio 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3074970
求助须知:如何正确求助?哪些是违规求助? 2728319
关于积分的说明 7503288
捐赠科研通 2376446
什么是DOI,文献DOI怎么找? 1260052
科研通“疑难数据库(出版商)”最低求助积分说明 610789
版权声明 597117