CLOCKWORK

Work around the Clock: effects of shift work on cognitive performance and circadian organization in behavior and physiology

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 Obiettivo del progetto (Objective)

'The 24-h organization of modern economy challenges the daily organization of our internal biological rhythms. Under normal conditions, an orchestra of body clocks, conducted by a central pacemaker in the hypothalamus (suprachiasmatic nucleus, SCN) synchronizes specific behavior and physiology to specific times of day, leading to optimal performance. Shift work conditions may reduce synchrony among body clocks, possibly leading to abnormal physiology and reduced cognitive function. Psychological stress, altered hormone levels, cancer risk, and obesity symptoms in shift workers indicate considerable consequences of internal physiological asynchrony. In this project we will keep mice under different shift work schedules to describe the mechanisms of physiological asynchrony and its consequences. Under normal light dark (LD) cycles, neuronal SCN activity is synchronized to the light, while mice are active and feed during the dark phase. Under shift work conditions, we will force feeding and/or locomotor activity in three shifts over the LD cycle. Behavioral, physiological, metabolic, and cognitive effects will be measured in mice exposed to fast advancing, slow advancing, fast delaying, and slow delaying schedules. At the end of a shift, a metabolic balance profile will be established. Electrophysiological SCN activity phase will be measured in vitro, and mice will be assessed for behavioral and feeding rhythms, for liver activity rhythm (bile acids and enzyme metabolites), and melatonin profiles. This circadian hormone was found at lower levels in shift workers and was correlated with their cancer prevalence. To assess the effects of shift work on psychological stress and cognitive performance, mice will be tested for maze learning and anxiety. The combined description of behavioral and physiological effects will provide strong insights in the impact of different shift work schedules on central and peripheral circadian organisation and cognitive performance.'

Introduzione (Teaser)

The 24-hour society takes its toll on those working irregular hours by affecting the body's internal biological rhythms, according to results from the EU-funded Clockwork project. The consortium has developed a mouse-based model to study the effect of shift working on mental performance and the body's biological clocks.

Descrizione progetto (Article)

Shift working is now common practice, but surprisingly little is known about its affect at the physiological and neurobiological level. Human beings have evolved internal biological rhythms that are adapted to a night-day cycle - circadian rhythm - but these can be disrupted by artificial lighting and long-haul flights. However, the greatest disruption to the synchronisation of the body's internal rhythm is caused by shift working.

Under normal conditions the body's internal clocks are controlled by a central pacemaker known as the suprachiasmatic nucleus (SCN) that is located in the hypothalamus region of the brain. The SCN synchronises certain behavioural and physiological responses according to specific times of day. This synchronisation enables an individual to operate at an optimum physiological and mental level. Loss of synchronisation due to shift working can lead to an abnormal physiological response such as obesity, reduced mental ability and an increase in disease.

Researchers from the Clockwork project have developed a comprehensive model for shift work using mice, which can describe the internal desynchronisation between the SCN and hormonal rhythms. The mice have been kept at different shift work schedules. Under normal light-dark cycles the rodents were active and feeding during the dark cycle, while SCN activity was synchronised with the light. Under shift work conditions feeding and forced activity were carried out in three shifts over the LD cycle.

Project partners have studied the central nervous system and SCN of the mice and their metabolism and physiology following exposure to the different work schedules. Scientists also investigated rhythms in the peripheral organs of the mice and their behaviour and mental performance.

Findings revealed that the LD cycle and the mice's metabolism were linked. Mice that were normally active during the night and sleeping during the day became active in the day and sleeping at night. This was not due to the central circadian clock (SCN) changing its pattern of activity, but due to its loss of influence on a, yet unknown, circadian pacemaker that drives activity.