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• W3203609797 abstract "• Paclitaxel lengthens wheel running rhythms in constant darkness. • Paclitaxel alters clock gene rhythmicity in the SCN and multiple brain regions. • Paclitaxel elevates circulating corticosterone and ablates its rhythmicity. • Paclitaxel dysregulates the amplitude of circadian genes in the adrenal glands . • Paclitaxel causes lasting SCN pro-inflammatory cytokine and chemokine secretion. Cancer patients experience circadian rhythm disruptions in activity cycles and cortisol release that correlate with poor quality of life and decreased long-term survival rates. However, the extent to which chemotherapy contributes to altered circadian rhythms is poorly understood. In the present study, we examined the extent to which paclitaxel, a common chemotherapy drug, altered entrained and free-running circadian rhythms in wheel running behavior, circulating corticosterone, and circadian clock gene expression in the brain and adrenal glands of tumor-free mice. Paclitaxel injections delayed voluntary wheel running activity onset in a light–dark cycle (LD) and lengthened the free-running period of locomotion in constant darkness (DD), indicating an effect on inherent suprachiasmatic nucleus (SCN) pacemaker activity. Paclitaxel attenuated clock gene rhythms in multiple brain regions in LD and DD. Furthermore, paclitaxel disrupted circulating corticosterone rhythms in DD by elevating its levels across a 24-hour cycle, which correlated with blunted amplitudes of Arntl , Nr1d1 , Per1 , and Star rhythms in the adrenal glands. Paclitaxel also shortened SCN slice rhythms, increased the amplitude of adrenal gland oscillations in PER2::luciferase cultures, and increased the concentration of pro-inflammatory cytokines and chemokines released from the SCN. These findings indicate that paclitaxel disrupts clock genes and behavior driven by the SCN, other brain regions, and adrenal glands, which were associated with chemotherapy-induced inflammation. Together, this preclinical work demonstrates that chemotherapy disrupts both central and peripheral circadian rhythms and supports the possibility that targeted circadian realignment therapies may be a novel and non-invasive way to improve patient outcomes after chemotherapy." @default.
• W3203609797 created "2021-10-11" @default.
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• W3203609797 date "2022-01-01" @default.
• W3203609797 modified "2023-10-14" @default.
• W3203609797 title "Paclitaxel chemotherapy disrupts behavioral and molecular circadian clocks in mice" @default.
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• W3203609797 doi "https://doi.org/10.1016/j.bbi.2021.09.011" @default.
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