分析小鼠昼夜节律变化的行为学方法

doi:10.16288/j.yczz.22-051

遗传 ›› 2022, Vol. 44 ›› Issue (4): 346-357.doi: 10.16288/j.yczz.22-051

• 技术与方法 • 上一篇

分析小鼠昼夜节律变化的行为学方法

曾义准(), 张陶, 徐璎

苏州大学苏州医学院,剑桥-苏大基因组资源中心,苏州 215123

收稿日期:2022-02-23 修回日期:2022-03-30 出版日期:2022-04-20 发布日期:2022-04-08
作者简介:曾义准,本科,专业方向：细胞生物学。E-mail: 20194250014@stu.suda.edu.cn
基金资助:
国家自然科学基金项目资助编号(31630091,32100931)

Rapid assessment of circadian behavior in mice

Yizhun Zeng(), Tao Zhang, Ying Xu

Cambridge-Su Genomic Resource Center, Suzhou Medical College of Soochow University, Suzhou 215123, China

Received:2022-02-23 Revised:2022-03-30 Online:2022-04-20 Published:2022-04-08
Supported by:
Supported by the National Natural Science Foundation of China Nos(31630091,32100931)

摘要/Abstract

摘要：

昼夜节律是指生命活动以24小时为周期的内在性节律。为了适应昼夜环境周期性的变化,地球上几乎所有生物体,包括藻类、细菌、植物、动物等,都演化出一个特殊的系统——生物钟,用以指挥不同组织与器官来适应环境的昼夜交替,维持机体的生理稳态和行为与环境昼夜变化同步。生物钟是指由内源性分子时钟控制的日周生理振荡过程,人类生命活动的各个层面,包括行为、生理、代谢等都受到生物钟的调控,并表现出明显的昼夜节律,如睡眠与苏醒、警觉程度与运动能力、体温波动、泌尿系统、激素分泌、免疫调节以及细胞因子释放等。昼夜节律紊乱可能影响各种疾病的发生、发展、治疗和预后。因此在机体的发育、衰老及疾病的发生、发展过程中评估昼夜节律是否异常具有重要的意义。结合本课题组相关研究,本文较为系统性地讨论了几种适用不同目的鉴别昼夜节律行为异常的方法,分享了具体的实验操作以及分析思路,包括利用代谢笼测量活动节律、自由跑轮活动监测、倒时差、长光照、骨骼光周期以及T7-cycle,并解释了不同行为学方法背后的生理意义。除此之外,本文还探究了不同遗传背景以及不同来源小鼠的昼夜节律在适应外界环境变化上的可能差异,为相关研究提供了可行的参考。根据这些原则及方法,以期帮助相关科研人员选择合适的实验来评估遗传因素、环境因素或疾病对昼夜节律行为的影响。

关键词: 昼夜节律, 代谢笼, 跑轮, 测量方法

Abstract:

Circadian rhythms have a cycle length of about 24 hours, i.e. a 24-hour internal clock. In order to adapt to the periodic changes of the circadian environment, almost all organisms on the earth, including algae, bacteria, plants, animals, etc., have evolved a special system—the circadian clock. It helps organisms to adapt to the daily changes in the environment and maintains the physiological process and the behavior in synchronization with the environment changes. Circadian rhythms are composed of an intracellular feedback loop that drives the expression of molecular components and their constitutive protein products to oscillate over a period of about 24 hours. Almost every aspect of the body's functions, including behavior and physiology, is regulated by the circadian clock, and shows obvious daily rhythms, such as sleep and wakefulness, alertness, body temperature fluctuations, urinary system, hormone secretion, immune regulation, and cytokine release. Circadian factors are also increasingly recognized for potentially affecting the occurrence, progression, treatment, and prognosis of a variety of diseases. This paper discusses several methods for measuring circadian behavior disorders in mice for different purposes, and shares experimental operations and analysis ideas, including the use of metabolism cage, wheel running activity, jet lag, lengthened light, bones photoperiod, as well as the T7-cycle. In addition, this paper also studies the possible reasons for variations caused by genetic backgrounds and light conditions. Given these methods, researchers can choose appropriate experiments to evaluate the influence of genetic factors, environmental factors or diseases on circadian behavior.

Key words: circadian rhythm, metabolism cage, wheel running, measuring method

曾义准, 张陶, 徐璎. 分析小鼠昼夜节律变化的行为学方法[J]. 遗传, 2022, 44(4): 346-357.

Yizhun Zeng, Tao Zhang, Ying Xu. Rapid assessment of circadian behavior in mice[J]. Hereditas(Beijing), 2022, 44(4): 346-357.

图/表 11

图1

图2

图3

图4

图5

图6

图7

图8

附图1

附图2

附图3

参考文献 34

[1]	Ruan W, Yuan XY, Eltzschig HK. Circadian rhythm as a therapeutic target. Nat Rev Drug Discov, 2021, 20(4):287-307. doi: 10.1038/s41573-020-00109-w pmid: 33589815
[2]	Pilorz V, Astiz M, Heinen KO, Rawashdeh O, Oster H. The concept of coupling in the mammalian circadian clock network. J Mol Biol, 2020, 432(12):3618-3638. doi: 10.1016/j.jmb.2019.12.037
[3]	Yue M, Yang Y, Guo GL, Qin XM. Genetic and epigeneticregulations of mammalian circadian rhythms. Hereditas (Beijing), 2017, 39(12):1122-1137.
	岳敏, 杨禹, 郭改丽, 秦曦明. 哺乳动物生物钟的遗传和表观遗传研究进展. 遗传, 2017, 39(12):1122-1137.
[4]	Arendt J. Shift work: coping with the biological clock. Occup Med (Lond), 2010, 60(1):10-20. doi: 10.1093/occmed/kqp162
[5]	Yuan L, Li YR, Xu XD. Chronobiology—2017 Nobel prize in physiology or medicine. Hereditas(Beijing), 2018, 40(1):1-11. doi: 10.16288/j.yczz.17-397 pmid: 29367188
	袁力, 李艺柔, 徐小冬. 时间生物学—2017年诺贝尔生理或医学奖解读. 遗传, 2018, 40(1):1-11. doi: 10.16288/j.yczz.17-397 pmid: 29367188
[6]	Scheiermann C, Gibbs J, Ince L, Loudon A. Clocking in to immunity. Nat Rev Immunol, 2018, 18(7):423-437. doi: 10.1038/s41577-018-0008-4 pmid: 29662121
[7]	Costello HM, Gumz ML. Circadian rhythm, clock genes, and hypertension: recent advances in hypertension. Hypertension, 2021, 78(5):1185-1196. doi: 10.1161/HYPERTENSIONAHA.121.14519
[8]	Mehra R. Sleep apnea and the heart. Cleve Clin J Med, 2019, 86(9 Suppl 1):10-18.
[9]	Daios S, Savopoulos C, Kanellos I, Goudis CA, Nakou I, Petalloti S, Hadjidimitriou N, Pilalas D, Ziakas A, Kaiafa G. Circadian pattern of acute myocardial infarction and atrial fibrillation in a mediterranean country: a study in diabetic patients. Medicina (Kaunas), 2021, 57(1):41.
[10]	Knutsson A. Methodological aspects of shift-work research. Chronobiol Int, 2004, 21(6):1037-1047. pmid: 15646248
[11]	Fagiani F, Di Marino D, Romagnoli A, Travelli C, Voltan D, Di Cesare Mannelli L, Racchi M, Govoni S, Lanni C. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct Target Ther, 2022, 7(1):41. doi: 10.1038/s41392-022-00899-y
[12]	Roenneberg T, Merrow M. The circadian clock and human health. Curr Biol, 2016, 26(10):R432-R443. doi: 10.1016/j.cub.2016.04.011
[13]	Pan XY, Mota S, Zhang BY. Circadian clock regulation on lipid metabolism and metabolic diseases. Adv Exp Med Biol, 2020, 1276:53-66.
[14]	Jagannath A, Taylor L, Wakaf Z, Vasudevan SR, Foster RG. The genetics of circadian rhythms, sleep and health. Hum Mol Genet, 2017, 26(R2):R128-R138. doi: 10.1093/hmg/ddx240
[15]	Honma S. Development of the mammalian circadian clock. Eur J Neurosci, 2020, 51(1):182-193. doi: 10.1111/ejn.14318 pmid: 30589961
[16]	Dannerfjord AA, Brown LA, Foster RG, Peirson SN. Light input to the mammalian circadian clock. Methods Mol Biol, 2021, 2130:233-247. doi: 10.1007/978-1-0716-0381-9_18 pmid: 33284449
[17]	Jagannath A, Varga N, Dallmann R, Rando G, Gosselin P, Ebrahimjee F, Taylor L, Mosneagu D, Stefaniak J, Walsh S, Palumaa T, Di Pretoro S, Sanghani H, Wakaf Z, Churchill GC, Galione A, Peirson SN, Boison D, Brown SA, Foster RG, Vasudevan SR. Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice. Nat Commun, 2021, 12(1):2113. doi: 10.1038/s41467-021-22179-z pmid: 33837202
[18]	Yamaguchi Y, Murai I, Goto K, Doi S, Zhou HH, Setsu G, Shimatani H, Okamura H, Miyake T, Doi M. Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock. Sci Rep#, 2021, 11(1): 22406. doi: M
[19]	Buhr ED, Vemaraju S, Diaz N, Lang RA, Van Gelder RN. Neuropsin (OPN5) mediates local light-dependent induction of circadian clock genes and circadian photoentrainment in exposed murine skin. Curr Biol, 2019, 29(20): 3478- 3487.e4.
[20]	Jagannath A, Taylor L, Wakaf Z, Vasudevan SR, Foster RG. The genetics of circadian rhythms, sleep and health. Hum Mol Genet, 2017, 26(R2):R128-R138. doi: 10.1093/hmg/ddx240
[21]	Zhang T, Xie PC, Dong YY, Liu ZW, Zhou F, Pan DJ, Huang ZY, Zhai QC, Gu Y, Wu QY, Tanaka N, Obata Y, Bradley A, Lelliott CJ, Sanger Institute Mouse Genetics Project, Nutter LMJ, McKerlie C, Flenniken AM, Champy MF, Sorg T, Herault Y, De Angelis MH, Durner VG, Mallon AM, Brown SDM, Meehan T, Parkinson HE, Smedley D, Lloyd KCK, Yan J, Gao X, Seong JK, Wang CKL, Sedlacek R, Liu Y, Rozman J, Yang L, Xu Y. High- throughput discovery of genetic determinants of circadian misalignment. PLoS Genet, 2020, 16(1):e1008577. doi: 10.1371/journal.pgen.1008577
[22]	Liu ZW, Huang ML, Wu X, Shi GS, Xing LJ, Dong Z, Qu ZP, Yan J, Yang L, Panda S, Xu Y. PER1 phosphorylation specifies feeding rhythm in mice. Cell Rep, 2014, 7(5):1509-1520. doi: 10.1016/j.celrep.2014.04.032
[23]	Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS. Mutagenesis and mapping of a mouse gene, clock, essential for circadian behavior. Science, 1994, 264(5159):719-725. doi: 10.1126/science.8171325 pmid: 8171325
[24]	Armstrong SM, Cassone VM, Chesworth MJ, Redman JR, Short RV. Synchronization of mammalian circadian rhythms by melatonin. J Neural Transm Suppl, 1986, 21:375-394.
[25]	Metzger J, Wicht H, Korf HW, Pfeffer M. Seasonal variations of locomotor activity rhythms in melatonin- proficient and -deficient mice under seminatural outdoor conditions. J Biol Rhythms, 2020, 35(1):58-71. doi: 10.1177/0748730419881922
[26]	Kurien P, Hsu PK, Leon J, Wu D, McMahon T, Shi GS, Xu Y, Lipzen A, Pennacchio LA, Jones CR, Fu YH, Ptáček LJ. TIMELESS mutation alters phase responsiveness and causes advanced sleep phase. Proc Natl Acad Sci USA, 2019, 116(24):12045-12053. doi: 10.1073/pnas.1819110116
[27]	Izumo M, Pejchal M, Schook AC, Lange RP, Walisser JA, Sato TR, Wang XZ, Bradfield CA, Takahashi JS. Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant. eLife, 2014, 3:e04617. doi: 10.7554/eLife.04617
[28]	So much more to know. Science, 2005, 309(5731):78-102.
[29]	Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB. A circadian gene expression atlas in mammals: implications for biology and medicine. Proc Natl Acad Sci USA, 2014, 111(45):16219-16224. doi: 10.1073/pnas.1408886111
[30]	Bass J, Lazar MA. Circadian time signatures of fitness and disease. Science, 2016, 354(6315):994-999. doi: 10.1126/science.aah4965
[31]	Verlande A, Masri S. Circadian clocks and cancer: timekeeping governs cellular metabolism. Trends Endocrinol Metab, 2019, 30(7):445-458. doi: 10.1016/j.tem.2019.05.001
[32]	Chellappa SL, Vujovic N, Williams JS, Scheer FAJL. Impact of circadian disruption on cardiovascular function and disease. Trends Endocrinol Metab, 2019, 30(10):767-779. doi: 10.1016/j.tem.2019.07.008
[33]	Jud C, Schmutz I, Hampp G, Oster H, Albrecht U. A guideline for analyzing circadian wheel-running behavior in rodents under different lighting conditions. Biol Proced Online, 2005, 7:101-116. doi: 10.1251/bpo109
[34]	Pan XY, Taylor MJ, Cohen E, Hanna N, Mota S. Circadian clock, time-restricted feeding and reproduction. Int J Mol Sci, 2020, 21(3):831. doi: 10.3390/ijms21030831

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

分析小鼠昼夜节律变化的行为学方法

Rapid assessment of circadian behavior in mice

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 11

参考文献 34

相关文章 2

编辑推荐

Metrics

[1]	曹英萍，石金磊，李钟，明凤. 水稻OsFAD2、OsFAD6的克隆及其家族成员对非生物胁迫的响应[J]. 遗传, 2010, 32(8): 839-847.
[2]	李经才，于多，王芳，何颖. 生物钟基因研究新进展[J]. 遗传, 2004, 26(1): 89-96.