Circadian disruption in mice through chronic jet lag-like conditions modulates molecular profiles of cancer in nucleus accumbens and prefrontal cortex. (20th February 2021)

• Record Type: Journal Article
• Authors: Khan, Suliman; Yong, V Wee; Xue, Mengzhou
• Is Part Of: Carcinogenesis. Volume 42:Number 6(2021)
• Page Start: 864
• Page End: 873
• Publication Date: 2021-02-20
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgab012
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: Biological rhythms regulate physiological activities. Shiftwork disrupts normal circadian rhythms and may increase the risk of cancer through unknown mechanisms. To mimic environmental light/dark changes encountered by shift workers, a protocol called 'chronic jet lag (CJL)' induced by repeatedly shifting light–dark cycles has been used. Here, we subjected mice to CJL by advancing light–dark cycle by 6 h every 2 days, and conducted RNA sequencing to analyze the expression profile and molecular signature in the brain areas of prefrontal cortex and nucleus accumbens. We also performed positron emission tomography (PET) imaging to monitor changes related to glucose metabolism in brain. Our results reveal systematic reprogramming of gene expression associated with cancer-related pathways and metabolic pathways in prefrontal cortex and nucleus accumbens. PET imaging indicates that glucose uptake level was significantly reduced in whole brain as well as the individual brain regions. Moreover, qPCR analysis describes that the expression levels of cancer-related genes were altered in prefrontal cortex and nucleus accumbens. Overall, these results suggest a molecular and metabolic link with CJL-mediated cancer risk, and generate hypotheses on how CJL increases the susceptibility to cancer. Abstract : In mice, chronic jet lag-like conditions produce in brain regions transcriptomic changes that are linked to the development of cancer. Brain glucose metabolism is also disrupted, highlighting the link between persistent disruption of circadian rhythm and brain carcinogenesis.