Unfixed light pattern-related circadian disruption impairs circadian-orexinergic-serotoninergic system and induces depression-like behaviors in mice.

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-07-11 DOI:10.1016/j.taap.2025.117464

Qianyi Liu, Qinghe Meng, Jingbo Qi, Jiaqi Cheng, Jianjun Jiang, Lanqin Shang, Xuetao Wei, Weidong Hao

{"title":"Unfixed light pattern-related circadian disruption impairs circadian-orexinergic-serotoninergic system and induces depression-like behaviors in mice.","authors":"Qianyi Liu, Qinghe Meng, Jingbo Qi, Jiaqi Cheng, Jianjun Jiang, Lanqin Shang, Xuetao Wei, Weidong Hao","doi":"10.1016/j.taap.2025.117464","DOIUrl":null,"url":null,"abstract":"<p><p>Unfixed light pattern (ULP) occurring in shift work can lead to circadian disruption (CD), which has been linked to the increasing risk of depression. However, whether ULP-related CD is a risk factor for depression has remained elusive and the underlying mechanism is poorly understood. In this study, mice were subjected to ULP-related CD and we found that CD mice showed prolonged immobility time in the tail suspension test and forced swimming test. This affective damage effect was exacerbated with a longer duration of CD and was reversed by recovery of CD. Mechanistically, it was demonstrated that expression of clock genes in the suprachiasmatic nucleus (SCN), lateral hypothalamus area (LHA), and dorsal raphe nucleus (DRN) showed different degrees of phase shift and arrhythmicity in CD mice during desynchronization period. Furthermore, we found phase shift but normal amplitude for the expression of SCN cFOS, and mesor decrease and phase shift for the expression of the downstream of SCN--LHA OX-A, DRN OX-A, and DRN 5-HT in mice during desynchronization period, which worsened with longer CD duration and restored after recovery of CD. Altogether, this study suggests that ULP-related CD may be a risk factor for depression and the circadian-orexinergic-serotoninergic pathway might involve in it, which may provide new insights for the prevention and treatment of depression induced by ULP-related CD occurring in shift work.</p>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117464"},"PeriodicalIF":3.3000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.taap.2025.117464","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Unfixed light pattern (ULP) occurring in shift work can lead to circadian disruption (CD), which has been linked to the increasing risk of depression. However, whether ULP-related CD is a risk factor for depression has remained elusive and the underlying mechanism is poorly understood. In this study, mice were subjected to ULP-related CD and we found that CD mice showed prolonged immobility time in the tail suspension test and forced swimming test. This affective damage effect was exacerbated with a longer duration of CD and was reversed by recovery of CD. Mechanistically, it was demonstrated that expression of clock genes in the suprachiasmatic nucleus (SCN), lateral hypothalamus area (LHA), and dorsal raphe nucleus (DRN) showed different degrees of phase shift and arrhythmicity in CD mice during desynchronization period. Furthermore, we found phase shift but normal amplitude for the expression of SCN cFOS, and mesor decrease and phase shift for the expression of the downstream of SCN--LHA OX-A, DRN OX-A, and DRN 5-HT in mice during desynchronization period, which worsened with longer CD duration and restored after recovery of CD. Altogether, this study suggests that ULP-related CD may be a risk factor for depression and the circadian-orexinergic-serotoninergic pathway might involve in it, which may provide new insights for the prevention and treatment of depression induced by ULP-related CD occurring in shift work.

查看原文本刊更多论文

不固定的光照模式相关的昼夜节律中断损害了小鼠的昼夜节律-食欲能-血清素能系统并诱发抑郁样行为。

轮班工作中出现的不固定光照模式（ULP）会导致昼夜节律紊乱（CD），这与抑郁症风险增加有关。然而，ulp相关的CD是否是抑郁症的危险因素仍然难以捉摸，其潜在机制也知之甚少。在本研究中，我们对小鼠进行了ulp相关的CD，我们发现CD小鼠在悬尾试验和强迫游泳试验中出现了长时间的静止不动。这种情感性损伤效应随着CD持续时间的延长而加剧，并随着CD的恢复而逆转。机制上表明，在去同步期间，CD小鼠视交叉上核（SCN）、下丘脑外侧区（LHA）和中隔背核（DRN）中的时钟基因表达表现出不同程度的相移和心律失常。此外，我们发现小鼠在去同步期SCN cFOS的表达出现相移但振幅正常，SCN下游LHA OX-A、DRN OX-A和DRN 5-HT的表达减少且相移，且随CD持续时间的延长而恶化，在CD恢复后恢复。本研究提示，ulp相关性CD可能是抑郁症的危险因素，可能与昼夜节律-食欲能-血清素能通路有关。这可能为预防和治疗轮班工作中ulp相关CD引起的抑郁提供新的见解。

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分钟内获得全文求助全文

来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.