PhD defence
Sleep and circadian rhythms: The effects of ketamine, caffeine and anthracyclines
- Y. Wang
- Date
- Wednesday 18 October 2023
- Time
- Location
-
Academy Building
Rapenburg 73
2311 GJ Leiden
Supervisor(s)
- Prof.dr. J. H. Meijer
- dr. T. de Boer
Summary
This thesis delves into the intricate relationship between the circadian timing system and sleep regulation, investigating the impact of various pharmacological interventions on these systems using two murine models. The first model involves Brown Norway rats, chosen for their representativeness due to their pigmented nature. This research explores how caffeine, sleep deprivation, and ketamine affect sleep and circadian-controlled activity in constant darkness conditions. Specifically, it uncovers that acute caffeine administration leads to a two-day reduction in REM sleep and increased neuronal activity in the lateral hypothalamus. Moreover, a comparison between sleep deprivation and acute ketamine administration, reveals shared effects on sleep patterns, particularly in NREM sleep, potentially linked to antidepressant mechanisms. The cancer-related fatigue mouse model, showing the influence of anthracycline drugs on fatigue symptoms, sleep architecture, and circadian rhythms. The results highlight that fatigue is more related to disrupted circadian rhythms than altered sleep duration. The follow-up experiment demonstrates the impact of doxorubicin on the master circadian clock and surrounding areas, revealing an internal misalignment that contributes to disrupted circadian behavior.
This thesis contributes to understanding how caffeine, ketamine, sleep deprivation, and anthracycline drugs affect sleep-wake regulation and the circadian timing system. The findings emphasize the interconnectedness of these systems and provide insights into potential therapeutic avenues for addressing antidepressant effects and cancer-related fatigue. The research underscores the significance of maintaining proper sleep and circadian rhythms for overall health and its relevance to various diseases in modern society.
PhD dissertations
Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
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