Circadian genes period1b and period2 differentially regulate inflammatory responses in zebrafish

Ren, Da-long; Zhang, Junlong; Yang, Lei-qing; Wang, Xiaobo; Wang, Zongyi; Huang, Di; Tian, Chen; Hu, Bing

doi:10.1016/j.fsi.2018.03.048

Cited by 30 publications

(11 citation statements)

References 42 publications

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“…It has been shown that overexpression of Cry1 significantly decreases inflammation in atherosclerotic mice ( 59 ), whereas the absence of Cry1 and Cry2 leads to increased pro-inflammatory cytokine expression in macrophages ( 60 ). Per2 negatively regulates the expression of pro-inflammatory cytokines in zebrafish ( 61 ). Bmal1 deficiency-induced the increased gene expression of Cry1 , Cry2 , and Per2 may also contribute to the reduced inflammation of Bmal1 KO microglial cells.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of the Circadian Clock Gene Bmal1 Reduces Microglial Immunometabolism

et al. 2020

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Microglia are brain immune cells responsible for immune surveillance. Microglial activation is, however, closely associated with neuroinflammation, neurodegeneration, and obesity. Therefore, it is critical that microglial immune response appropriately adapts to different stressors. The circadian clock controls the cellular process that involves the regulation of inflammation and energy hemostasis. Here, we observed a significant circadian variation in the expression of markers related to inflammation, nutrient utilization, and antioxidation in microglial cells isolated from mice. Furthermore, we found that the core clock gene-Brain and Muscle Arnt-like 1 (Bmal1) plays a role in regulating microglial immune function in mice and microglial BV-2 cells by using quantitative RT-PCR. Bmal1 deficiency decreased gene expression of pro-inflammatory cytokines, increased gene expression of antioxidative and anti-inflammatory factors in microglia. These changes were also observed in Bmal1 knock-down microglial BV-2 cells under lipopolysaccharide (LPS) and palmitic acid stimulations. Moreover, Bmal1 deficiency affected the expression of metabolic associated genes and metabolic processes, and increased phagocytic capacity in microglia. These findings suggest that Bmal1 is a key regulator in microglial immune response and cellular metabolism.

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Section: Discussionmentioning

confidence: 99%

Deficiency of the Circadian Clock Gene Bmal1 Reduces Microglial Immunometabolism

et al. 2020

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“…Given that oscillations of cry1aa and per1b show a phase shift upon treatment with NMR, while the oscillation of per2 remains stable, this should also lead to altered ratios of the protein heterodimers Cry1aa/Per1b and Cry1aa/Per2 in the cytosol of cells. Consequently, also different gene sets should be activated or repressed according to the type of irradiation, in particular when considering that zebrafish per2 is predominantly and essentially involved in the positive regulation of the circadian clock, while per1b exerts a repressive function (Wang et al 2015), and that both play also differential roles in the inflammatory immune response of zebrafish (Ren et al 2018), implicating therefore also an immunomodulatory capacity of NMR irradiation. Interestingly, NMR therapy applied for 4 h did not affect the oscillating promoter activity of per1b ( Figure S4), so that response elements located in the first 3.1 kb of the per1b promoter regions can be excluded from being responsible for the NMR-induced alterations at the level of per1b mRNA.…”

Section: Discussionmentioning

confidence: 99%

Nuclear magnetic resonance affects the circadian clock and hypoxia-inducible factor isoforms in zebrafish

Oliva

Jansen

Benscheidt

et al. 2018

Biological Rhythm Research

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Nuclear magnetic resonance (NMR) is used for magnetic resonance imaging and, at a lower intensity, as therapy for the treatment of musculoskeletal disorders. Due to the involvement of the circadian clock protein CRYPTOCHROME in the magnetic orientation of animals, it was repeatedly assumed that magnetic fields might affect the circadian rhythm of cells and organisms. Since circadian time keeping and hypoxic signaling are mutually intertwined, we investigated the effects of NMR on both cellular pathways in zebrafish fibroblast cells and larvae. In cells, basal mRNA expression of cryptochrome1aa was increased and oscillations of crypto-chrome1aa and period1b were shifted in phase, while those of clock1a and period2 remained unaffected. Similarly, circadian oscillations of cryptochrome1aa and period1b were restored in zebrafish larvae, while those of clock1a and period2 remained unaltered. NMR also restored the circadian expression of the hypoxia-inducible factor (Hif) isoforms Hif-1α and Hif-3α at the mRNA and protein level, but had no effect on the expression of Hif-2α. Thus, NMRmediated effects might differ substantially from the light-induced reset of the circadian clock in the same species and therefore represent an additional operation mode of the cellular clock, enabling distinct processing of photic and magnetic information.

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“…This indicates that zebrafish recognised stressors and initiated their adaptation mechanisms. Circadian rhythms regulate immune processes in an organism (Ren et al 2018 ), which can be adjusted due to chemical-mediated changes in internal homeostasis towards adaptation (Yang et al 2018 ). Cellular free radicals and the circadian clock are interconnected; thus, alterations in antioxidants’ defence mechanisms result in fish circadian disruption (Zheng et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…The swimming behaviour of a fish might affect under stress conditions. Thus, we can observe different stages (safe, acclimation, adjustment, or toxic) on the swimming response of fish (Ren et al 2018 ). These behavioural changes could result in hyper- or hypo-activity.…”

Section: Introductionmentioning

confidence: 99%

Assessment of eco-toxic effects of commonly used water disinfectant on zebrafish (Danio rerio) swimming behaviour and recovery responses: an early-warning biomarker approach

Ren

Ramesh

et al. 2022

Environ Sci Pollut Res

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Eco-toxicity profiles for commonly used disinfectants were lacking. Available traditional toxicity techniques have some limitations (assessments and ethical issues). Behaviour toxicology is a promising research area towards early warning and non-invasive approaches. We studied the potential eco-toxic effects of sodium hypochlorite (NaOCl) on the swimming behaviour of zebrafish. Zebrafish were exposed to different concentrations (Treatment I, Treatment II, Treatment III, and Treatment IV) of NaOCl for 360 h. Recovery study (144 h) was conducted for NaOCl treatment groups. The swimming behaviour of zebrafish was quantified efficiently using an online monitoring system (OMS). OMS dataset was processed for determination of behavioural differences by MATLAB and SPSS. Compared to the control group, the swimming strength of zebrafish under NaOCl treatments declined significantly ( p < 0.001). Avoidance behaviour has occurred on zebrafish under NaOCl exposure periods. Furthermore, NaOCl toxicity also adjusted circadian rhythms on zebrafish. Zebrafish swimming strength was significantly ( p < 0.001) improved under-recovery periods. Moreover, normal diurnal patterns have occurred. NaOCl could cause behavioural abnormalities in non-target organisms. Continuous exposure to common disinfectants could cause external and internal stress on non-target organisms, resulting in behavioural changes and circadian rhythm adjustments. Continuous changes in behavioural and circadian rhythms might reduce organisms’ fitness and adaptation capacity. This study highlights (1) the importance of computer-based toxicity assessments, and (2) swimming behaviour is an early warning biomarker for eco-toxicity studies. Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-18333-1.

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Circadian genes period1b and period2 differentially regulate inflammatory responses in zebrafish

Cited by 30 publications

References 42 publications

Deficiency of the Circadian Clock Gene Bmal1 Reduces Microglial Immunometabolism

Deficiency of the Circadian Clock Gene Bmal1 Reduces Microglial Immunometabolism

Nuclear magnetic resonance affects the circadian clock and hypoxia-inducible factor isoforms in zebrafish

Assessment of eco-toxic effects of commonly used water disinfectant on zebrafish (Danio rerio) swimming behaviour and recovery responses: an early-warning biomarker approach

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