on general health and life expectancy as the equivalent of smoking a pack of cigarettes a day! By the early seventies, the region of the mammalian brain responsible for circadian patterns of behaviour had been localised to a tiny structure, named the suprachiasmatic nucleus (SCN). The SCN comprises just 16,000 neurons, yet it appears to be both necessary and sufficient to account for circadian behaviour. Laboratory mice lacking the SCN have been shown to lose their circadian rhythms. In recent years, it has been shown that even single isolated SCN neurons can sustain an approximately 24-hour pattern of firing activity when cultured in a petri dish. Certain neurodegenerative diseases, such as Parkinson’s, can result in disruption of circadian rhythms through lesion of the SCN.These
patients have no temporal order to their day, which means that they require 24-hour care and supervision. Indeed, this is one of the primary reasons for the institutionalisation of those with advanced Parkinson’s disease. More recently, a small number of core ‘clock genes’ have been discovered through the study of animals with faulty versions of these genes (resulting in a clock running too fast, too slow, or not at all). Studies into a particular clock gene named Period2 have proved to be of particular interest. Mutations in this gene can lead people to suffer from a rare disorder in which patients have a 20-hour clock, causing them to wake at odd times. Interestingly, Period2 has also been identified as a tumour suppressor in humans. Scientists have deleted the Period2 gene from a mouse’s genome and observed its behaviour.A normal
mouse has an approximately 24-hour cycle of behaviour, even in the dark, whereas mice lacking Period2 cannot sustain a regular cycle without external time cues. Their clock has effectively stopped. Recent work suggests that many other cells in the body, in tissues besides the brain, can self-sustain their own circadian patterns of gene expression.The search is now on to discover to what extent the SCN controls rhythms in other tissues. Ultimately, circadian biologists hope to understand the clock well enough to allow us to better deal with the ravages of our 24-hour culture, and to fully unravel the health implications of our amazing, self-sustaining biological clocks. John O’Neill is a PhD student in the MRC Laboratory of Molecular Biology.
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