Scientists uncover "time for bed" molecules

Animals lacking molecules called cryptochromes have abnormal sleeping patterns because their internal biorhythms are disrupted. New research from scientists at Stanford University, the University of North Carolina and SRI International published in the open access journal, BMC Neuroscience shows that mice lacking these molecules also respond differently to sleep deprivation. This suggests that cryptochromes are also involved in sleep homeostasis, the process by which we feel tired after we have been awake for a long time.

Sleep is regulated in mammals in two ways. Firstly, it is controlled by an internal body clock, which in humans makes us feel tired at night and awake during the day. Secondly there is a tendency for animals deprived of sleep to feel tired and sleep longer following prolonged wakefulness. This is due to a process called sleep homeostasis, which tries to maintain a balance between time spent awake and time spent asleep.

Molecules known as cryptochromes are known to be involved in the generation of the natural rhythms of the body clock, but it is not clear if they are involved in the regulation of sleep after a period of wakefulness. Stanford scientists Dale Edgar, Jonathan Wisor and colleagues have now investigated the regulation of sleep in mice that are unable to produce functional cryptochrome molecules.

Mice are a nocturnal species that tend to sleep during the day and be awake at night. Mutant mice that lack the cryptochrome genes do not show a preference for sleep at night, which suggests that their body clocks are broken. To investigate the response of these mice to sleep deprivation the researchers continually woke mice up for six hours with gentle handling or by the introduction of an unfamiliar object into their cage.

The response of the mutant mice to being kept awake was quite different to normal mice. The researchers were able to measure both the intensity and length of non-REM sleep following sleep deprivation by measuring brain waves in a technique known as electroencephalography. After six hours of sleep deprivation normal mice showed a characteristic increase in the duration of sleep as regulated by homeostasis. However, mutant mice lacking cryptochromes did not exhibit increases in the duration of non-REM sleep following sleep deprivation.

These results led researchers to conclude that mice lacking cryptochromes can be used a model organism to gain a deeper understanding about the ways in which sleep is regulated. Further understanding of the process of sleep regulation is exciting as the disruption of normal sleeping patterns is a common symptom in a variety of illnesses ranging from arthritis to Parkinson’s disease as well a being very common in sufferers of depression.