Connection between expression of clock genes and sleep

Oct 18 2007

Genes responsible for our 24 hour body clock influence not only the timing of sleep, but also appear to be central to the actual restorative process of sleep, according to research published in the online open access journal BMC Neuroscience.

The study identified changes in the brain that lead to the increased desire and need for sleep during time spent awake.

"We still do not know why we benefit from sleep, or why we feel tired when we are 'lacking' sleep, but it seems likely that sleep serves some basic biological function for the brain such as energy restoration for brain cells or memory consolidation." Explains Dr Bruce O'Hara of the University of Kentucky, one of the neuroscientists who conducted the research. "We have found that clock gene expression in the brain is highly correlated to the build-up of sleep debt, while previous findings have linked these genes to energy metabolism. Together, this supports the idea that one function of sleep is related to energy metabolism."

To explore the connection between the expression of clock genes and sleep, three inbred strains of mice with different genetic make-ups were utilized, and which had previously been shown to differ in their response to sleep deprivation by lead author, Dr. Paul Franken of Stanford University and Lausanne University. In this study, mice were first sleep deprived during the daytime period when mice normally sleep then allowed recovery sleep. Changes in gene expression for three clock genes were examined throughout the brain during both phases. Clock gene expression generally increased the more the mice were kept awake and decreased when sleep was allowed, supporting that these genes play a role in the regulation of the need for sleep. Generally, the expression of the clock-genes Period-1 and Period-2, increased at a faster rate in mouse strains with the poorest quality of recovery sleep suggesting that the detailed dynamic changes in expression may underlie individual differences in sleep length and sleep quality. The changes in gene expression were also shown to occur in many different brain regions supporting the idea that sleep is a global brain function.

A handful of genes such as Period-1 and Period-2 have been shown previously to underlie our circadian rhythms (behavior and physiology that follow a 24 hour cycle). The major advantage of circadian rhythms is that they allow animals and plants to predict and prepare for periodic changes in the environment. The anticipatory increase in clock-gene expression may be, on a molecular level, an animal's preparation for activity. Variations in clock genes may underlie rhythmic traits influencing our preferred wake-up time, but the clock genes' role in direct sleep regulation, as shown in this study, may also influence sleep duration and human performance with differing amounts of sleep. The research could also help shed light on the biology of mood disorders, such as Seasonal Affective Disorder (SAD) or bipolar disorder, that appear linked to both sleep and circadian rhythms.