Nature's Journal Club

Martha Merrow

University of Groningen, the Netherlands

A chronobiologist makes sense of circadian dysfunction in illness.

When my grandfather was dying of cancer, he found himself up most nights with my grandmother, who was succumbing to Alzheimer’s disease. A nasty side effect of some neurodegenerative diseases is the loss of a regular sleep–wake cycle. Our circadian biological clock is manifest in every one of our cells, which show daily rhythms in gene expression; cellular clocks synchronise to become organ clocks, and these determine the whole organism clock.

When Jennifer Morton at the University of Cambridge, UK, and her colleagues investigated the timing of gene expression in tissues from mouse models of Huntington’s disease, they found daily ups and downs — at least in some genes — that were similar to those in healthy animals (E. Maywood et al. J. Neurosci. 30, 10199–10204; 2010). But the mice slept and woke at random even when exposed to regular light–dark cycles. Interestingly, the researchers found that rhythmic behaviour could be restored to Huntington’s mice through another stimulus — feeding the animals at a specific time of day.

I am intrigued by this work because it highlights the relevance of chronobiology to neurodegenerative disease. The authors show that in Huntington’s, the disease disrupts behavioural manifestation of the clock; in a bizarre feedback, the progression of the disease may be exacerbated by clock dysfunction through disruption in expression of a subset of clock-controlled genes.

This work also reminds me that non-photic clock stimuli are powerful tools and can be used to set the clock when light cannot. These alternatives will be important as we try to keep the clock synchronized in our increasingly unnatural modern environment — and as we try to improve the health and quality of life for both grandmothers and grandfathers


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