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OP.04 Circadian rhythms and their disorders
  1. K Wulff

    Katharina Wulff, PhD is currently a senior research scientist in Sleep and Circadian Neuroscience of the Nuffield Laboratory of Ophthalmology (NLO) at the University of Oxford. She studied biology in Berlin, Germany, and completed her PhD in chronobiology, studying the interactions between the well-established sleep-wake behaviour of parents and that of their developing newborn infants. The award of a EU Marie Curie Individual Fellowship allowed her to join the lab of Prof. Foster at Imperial College London in 2002, with whom she established new collaboration between his circadian molecular-focussed lab and labs with expertise in human sleep and psychiatry, linking basic circadian science with basic and clinical human research. Since then the lab moved to Oxford in 2007 where she is now leading the human chronobiology/sleep lab of the NLO.

Abstract

Circadian rhythms are daily cycles in physiology and behaviour that are driven by an endogenous oscillator with a period of approximately (circa) one day (diem). The suprachiasmatic nuclei (SCN) of the hypothalamus constitute the master-oscillator coordinating circadian rhythms in the brain and periphery and simultaneously adjusting its neuronal activity to the environmental light-dark cycle. When subjects are isolated from environmental time cues such as social interaction and the light-dark cycle the oscillator still continues to define “day-time” activity and “night-time” inactivity and circadian rhythms are expressed, albeit with a longer than 24-h period (free-run) in humans. The circadian oscillator anticipates time-of-day, thereby enabling our complex physiology to prepare to the contrasting demands by giving catabolic processes prevalence during the day to facilitate engagement with the world, and prevalence of anabolic functions to the night such as growth, repair and consolidation. These processes establish an internal temporal order that optimises their biological functioning. For example, core body temperature falls and melatonin is secreted in the evening to facilitate sleep. Secretion of growth hormone and prolactin is increased at the beginning of sleep, and activation of the adreno-corticotropic axis starts before waking in the early morning, thereby preparing the body for activities of the waking period. The recent finding of local circadian clocks in different brain areas such as hippocampus and cerebellum and peripheral organs such as liver, heart and kidneys, which utilise the same basic molecular components as the SCN, offers a completely new way of thinking about the role of circadian mechanisms in health and disease. The role of the SCN is to keep the local clocks in synchrony with each other and with the environmental light-dark cycle. When optimal circadian timing is disrupted, for example when sleep occurs at inappropriate stages of the circadian cycle due to shift work, jet lag, or as a consequence of psychiatric, neurological and neurodegenerative disease, attention, remembering, learning and emotional state are all compromised as a consequence of internal desynchronisation. There is a strong temporal relationship between optimal cognitive and emotional function and circadian regulation of peripheral and brain metabolism. Local clocks throughout the brain and periphery need to be considered as facilitators of circadian phase and sleep on emotional state and cognitive performance but also natural genetic variants of human clock genes are expected to have an effect on circadian and homeostatic sleep and other behaviours such as appetite and eating. Therefore the circadian system is likely to have a widespread influence on various behaviours not limited to sleep problems.

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