Sleep Europe 2024 Lecture Summary
The mechanisms underlying circadian misalignment, sleep restriction and metabolic disease are not fully understood. We have been investigating the potential of metabolic profiling (metabolomics), the large-scale study of metabolites, to uncover novel mechanisms and possible biomarkers of circadian disruption and sleep deprivation. Using controlled laboratory studies, the effect of sleep and total sleep deprivation on the human metabolome has been characterised. Moreover, whether 24-h metabolite rhythms in plasma are driven by exogenous, imposed factors such as feeding/fasting and sleep/wake and/or by the endogenous circadian timing system has been investigated. Characterising the effects of sleep and food timing on metabolite rhythms in healthy volunteers on normal sleep schedules using targeted LC-MS/MS metabolomics has provided the necessary baseline to our subsequent studies of the metabolomics of shift work.
Two approaches to perform metabolic profiling in shift work have been employed: 1. Simulated shift work protocols in controlled laboratory conditions and 2. Real-life workers doing rotating shifts. Simulated shift work allows light/dark, feeding/fasting and sleep/wake timings to be precisely controlled and multiple time-series samples to be collected under constant routine conditions. Our simulated shift work study showed that after 3 nights of working shifts, endogenous circadian rhythms of many plasma metabolites were misaligned from the central circadian clock timing by ~12 h (internal desynchrony) and instead aligned with the food and sleep timing of the prior shift schedule, likely reflecting the peripheral clocks’ response to mistimed behavioural cues.
Since there is a limit to the number of sequential blood samples that can be collected in field studies, we have recently tested an ambulatory microdialysis device, U-RHYTHM, capable of sampling human interstitial fluid metabolites every 20 minutes for up to 27 h. Targeted metabolomics analysis revealed interstitial fluid metabolite rhythms that correlated with the plasma metabolite rhythms, validating this approach.
In conclusion, misalignment between circulating metabolite rhythms and central circadian clock-driven rhythms (melatonin and cortisol) likely underlies the adverse metabolic consequences of working shifts. Metabolic profiling will be useful to track circadian misalignment in shift work and test management strategies. Combined with U-RHYTHM, a practical way of examining circadian/ultradian metabolite rhythms in real-life shift workers is now possible.
Prof. Dr. Sebastiaan Overeem
"Expanding the sleep monitoring toolbox"
Sleep is a dynamic process actively orchestrated by complex neurochemical signals. In this presentation, Dr. Xu will share his recent work exploring how brain neurochemical systems—particularly the norepinephrine and acetylcholine systems—contribute to memory consolidation and the regulation of distinct sleep stages. By examining the real-time dynamics of these neuromodulators and mapping their downstream neural circuits, Dr. Xu has uncovered previously unrecognized temporal windows during NREM sleep that are essential for memory consolidation. Within these time windows, specific subtypes of hippocampal interneurons play a critical role as key mediators of memory processing. In parallel, these studies have delineated new circuits that control the transition between NREM and REM sleep. Together, these findings provide a more cohesive understanding of how sleep sustains cognitive processes and suggest potential pathways for clinical applications in sleep-related disorders.
Keynote Speaker
Biography
Full Professor in the Biomedical Diagnostics Laboratory at Eindhoven University of Technology, where he leads the Advanced Sleep Monitoring group. His clinical work as a somnologist takes place at the Centre for Sleep Medicine Kempenhaeghe, also located in the south of the Netherlands.
His research focuses on the development, validation and implementation of new diagnostic and monitoring methods for sleep disorders.
Overeem has a broad interest and experience in the field of sleep medicine. His first contribution to the sleep field employed (neurophysiological) monitoring already, using H-reflexes to study the mechanisms underlying cataplexy. His Lancet paper on the phenomenon of ‘being weak with laughter’ received wide attention. His work on narcolepsy continued through a collaboration between Leiden University (his alma mater) and Stanford University, where he participated in the very first hypocretin studies.
He joined Eindhoven University of Technology in early 2015, where he established a new multidisciplinary group supporting close collaboration between basic (data) scientists and clinical researchers. Within the framework of the Eindhoven MedTech Innovation Centre, Overeem coordinates various research efforts aimed at improving the diagnosis of sleep disorders through new non-obtrusive measurement modalities, in addition to advanced sleep analysis methods. Besides objective measures, the assessment of subjective sleep experience and symptoms is an integral research topic.
Together with Paul Reading, Overeem is editor of the book Sleep Disorders in Neurology: A Practical Approach. He has published over 280 peer-reviewed papers.
He likes to spend his free time underwater or in the sky: he is an avid SCUBA diver at the Global Under Water Explores Tech level, and holds a Private Pilot License.