The circadian timing system is highly integrated with the sleep-wake regulation system. This thesis focuses on how different pharmacological treatments influence the sleep regulation system and the... Show moreThe circadian timing system is highly integrated with the sleep-wake regulation system. This thesis focuses on how different pharmacological treatments influence the sleep regulation system and the circadian timing rhythm in two murine models. In the first animal model, which is presented in Chapter 2 and 3, we implanted EEG/EMG electrodes in freely moving Brown Norway rats. We chose this rat strain because it is pigmented and therefore a more representative model than the more mainstream rat strains which are usually albino rats. This study aimed to investigate the effect of caffeine, sleep deprivation and ketamine on sleep and circadian-controlled activity under constant darkness. In the second animal model, which is presented in Chapter 4 and 5, we implanted EEG/EMG or Multi-unit electrodes in chemotherapy-induced fatigue mice. All the results from this thesis and future perspectives were discussed in Chapter 6. We are able to see how disruption of sleep and the circadian clock adversely affect health and may contribute to many diseases in modern society. In this thesis, these studies provide a better understanding of these drugs influence the circadian timing system and sleep-wake regulation and maybe new treatment approaches for antidepressant therapy and cancer related fatigue. Show less
The anthracycline drug doxorubicin, is one of the most used chemotherapeutic drugs, with over one million patients treated every year. However, the exact molecular mechanism by which this drug kill... Show moreThe anthracycline drug doxorubicin, is one of the most used chemotherapeutic drugs, with over one million patients treated every year. However, the exact molecular mechanism by which this drug kill tumor cells remain unclear. In addition, treatment with anthracyclines coincides with severe adverse effects such as cardiotoxicity, secondary tumor formation and gonadotoxicity. Understanding how these highly effective anticancer drugs function and why they cause these severe toxicities would have tremendous impact on cancer treatment and the quality of life of cancer survivors. Therefore, even today, studying old anticancer drugs has high therapeutic potential and opens new exciting paths to improve currently available treatment options. Show less
