Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 13:16:1031448.
doi: 10.3389/fninf.2022.1031448. eCollection 2022.

Chronic jet lag-like conditions dysregulate molecular profiles of neurological disorders in nucleus accumbens and prefrontal cortex

Rabeea Siddique  1   2 , Faryal Mehwish Awan  3 , Ghulam Nabi  4 , Suliman Khan  1   2   3 , Mengzhou Xue  1   2
Affiliations

Chronic jet lag-like conditions dysregulate molecular profiles of neurological disorders in nucleus accumbens and prefrontal cortex

Rabeea Siddique et al. Front Neuroinform. .

Abstract

Background: Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease including, cancer, psychiatric, and related brain diseases.

Results: In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice's brain. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the quantitative PCR (qPCR) analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL.

Conclusion: Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.

Keywords: alternating light-dark cycles; chronic jetlag (shiftwork); circadian rhythms; neurological diseases; serotonin.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chronic jetlag (CJL) mediated molecular alterations in the brain. Expression levels of a number of circadian clock-related genes were altered in mice exposed to CJL, indicating that the circadian clock was disrupted. In addition, metabolic pathways were also found altered in response to CJL. Moreover, pathways associated with important neurological diseases and biological functions were found affected by CJL.
FIGURE 2
FIGURE 2
Chronic jetlag (CJL) altered mRNA levels of genes associated with psychiatric disorders in the NAc. This figure shows mRNA levels in NAc extracts from baseline and CJL treated animals (n = 3 per group), as assayed by three independent qPCR assays, at four different time points (ZT1, ZT7, ZT13, and ZT19). Expression levels in CJL treated mice were normalized to selected expression levels in baseline mice at specific ZT. Results are expressed as mean ± SEM. *P < 0.01, two-way ANOVA.
FIGURE 3
FIGURE 3
Chronic jetlag (CJL) altered mRNA levels of genes associated with psychiatric disorders in the PFC. This figure shows mRNA levels in PFC extracts from baseline and CJL treated animals (n = 3 per group), as assayed by three independent qPCR assays, at four different time points (ZT1, ZT7, ZT13, and ZT19). Results are expressed as mean ± SEM. *P < 0.01, two-way ANOVA.
FIGURE 4
FIGURE 4
Chronic jetlag (CJL) altered mRNA levels of genes associated with psychiatric disorders in the hippocampus. This figure shows mRNA levels in hippocampus extracts from baseline and CJL treated animals (n = 3 per group), as assayed by three independent qPCR assays, at four different time points (ZT1, ZT7, ZT13, and ZT19). Results are expressed as mean ± SEM. *P < 0.01, two-way ANOVA.
FIGURE 5
FIGURE 5
Chronic jetlag (CJL) altered mRNA levels of genes associated with psychiatric disorders in the hypothalamus. This figure shows mRNA levels in hypothalamus extracts from baseline and CJL treated animals (n = 3 per group), as assayed by three independent qPCR assays, at four different time points (ZT1, ZT7, ZT13, and ZT19). Results are expressed as mean ± SEM. *P < 0.01, two-way ANOVA.
FIGURE 6
FIGURE 6
Chronic jetlag (CJL) altered mRNA levels of genes associated with psychiatric disorders in the striatum. This figure shows mRNA levels in striatum extracts from baseline and CJL treated animals (n = 3 per group), as assayed by three independent qPCR assays, at four different time points (ZT1, ZT7, ZT13, and ZT19). Results are expressed as mean ± SEM. *P < 0.01, two-way ANOVA.
FIGURE 7
FIGURE 7
Chronic jetlag (CJL) disrupts serotonin regulation in the brain. (A) CJL altered the levels of 5-HT receptors and transporters in the nucleus accumbens and prefrontal cortex (detected by RNA sequencing). All data are presented as means ± SEM, *P < 0.05. (B) CJL altered 5Htt mRNA in the raphe nucleus. This figure shows mRNA levels in raphe nucleus extracts from baseline and CJL treated animals (n = 3 per group), as assayed by three independent qPCR assays, at four different time points (ZT1, ZT7, ZT13, and ZT19). Results are expressed as mean ± SEM. **P < 0.01, ***P < 0.001, two-way ANOVA. Panel (C) represents levels (mean ng g– 1 wet weight ± SEM) of dopamine (5-HT) in the hippocampus, hypothalamus, striatum, frontal cortex, accumbens as determined by fluorospectrophotometry. *P < 0.05, **P < 0.01, ***P < 0.001 (n = 304), two-way ANOVA.
FIGURE 8
FIGURE 8
Chronic jetlag (CJL) increased corticosterone levels. This figure shows the plasma total corticosterone in C57/BL6 mice treated with phase advance CJL for 30 days, on four different time points (ZT1, ZT7, ZT13, and ZT19). Total corticosterone in a sample of tail blood was measured. All data are presented as means ± SEM, *P < 0.05, **P < 0.01, student’s t-test (n = 4).
See this image and copyright information in PMC

References

    1. Bollinger T., Schibler U. (2014). Circadian rhythms–From genes to physiology and disease. Swiss Med. Wkly. 144 1–11. - PubMed
    1. Carlson J., Depetro E., Maxwell J., Harmon-Jones E., Hajcak G. (2015). Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample. Psychiatry Res. Neuroimaging 233 285–288. 10.1016/j.pscychresns.2015.06.005 - DOI - PubMed
    1. Chu X., Zhou Y., Hu Z., Lou J., Song W., Li J., et al. (2016). 24-hour-restraint stress induces long-term depressive-like phenotypes in mice. Sci. Rep. 6:32935. 10.1038/srep32935 - DOI - PMC - PubMed
    1. Coleman R., Liang C., Patel R., Ali S., Mukherjee J. (2017). Brain and brown adipose tissue metabolism in transgenic Tg2576 mice models of Alzheimer disease assessed using18F-FDG PET imaging. Mol. Imaging 16 1–9. 10.1177/1536012117704557 - DOI - PMC - PubMed
    1. Crispim C., Waterhouse J., Dâmaso A., Zimberg I., Padilha H., Oyama L., et al. (2011). Hormonal appetite control is altered by shift work: A preliminary study. Metabolism 60 1726–1735. 10.1016/j.metabol.2011.04.014 - DOI - PubMed