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.. it appears to be in mainly about genetical clockwork. 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 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.

Source: Paul Franken, Ryan Thomason, H. Craig Heller and Bruce F O’Hara, “A non-circadian role for clock-genes in sleep homeostasis: a strain comparison”  BMC Neuroscience (in press)

see also:


CNS Neurol Disord Drug Targets. 2007 Feb;6(1):71-81.

 Genomic and proteomic approaches towards an understanding of sleep.

 O’Hara BF, Ding J, Bernat RL, Franken P.

Department of Biology, University of Kentucky, Lexington, KY 40506, USA.

The basic functions of sleep are still unclear, however, recent advances in genomics and proteomics have begun to contribute to our understanding of both normal and pathological sleep. In this review, we focus primarily on normal sleep and wake that have been studied in model organisms such as mice. Mice have been especially valuable since many different inbred strains exist that differ in sleep-related traits, and genes can be altered by either mutagenesis or targeted approaches. Advances in QTL (Quantitative Trait Loci) analysis have also helped to identify important sleep related genes, and several other QTLs have been mapped as a first step toward finding the genes that underlie basic sleep traits. In addition to more traditional genetic approaches, the abundance of different mRNAs across sleep and wake can now be studied and compared in different brain regions much more thoroughly using microarray methods. Progress at the protein level has been more difficult, but a few studies have begun to investigate changes in proteins during sleep and wake, and we present some of our own preliminary data in this area. A knowledge of which genes and proteins control or respond to changes in sleep will not only help answer fundamental questions, but may also suggest novel drug targets for improving multiple aspects of sleep and wake.

Written by huehueteotl

October 19, 2007 at 12:11 pm

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