Sleep deprivation increases A1 adenosine receptor binding in the human brain: A positron emission tomography study

Elmenhorst, D.; Haas, H. L.; Zilles, K.; Matusch, A.; Bauer, A.; Coenen, H. H.; Meyer, P. T.; Basheer, R.; Winz, O. H.; Ermert, J.

doi:10.1523/JNEUROSCI.5066-06.2007

Journal Article

Sleep deprivation increases A1 adenosine receptor binding in the human brain: A positron emission tomography study

Elmenhorst, D.FZJ* ; Meyer, P. T. ; Winz, O. H.FZJ* ; Matusch, A.FZJ* ; Ermert, J.FZJ* ; Coenen, H. H.FZJ* ; Basheer, R. ; Haas, H. L. ; Zilles, K.FZJ* ; Bauer, A.FZJ*

2007
Soc. Washington, DC

The journal of neuroscience 27, 2410 - 2415 (2007) [10.1523/JNEUROSCI.5066-06.2007]

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Please use a persistent id in citations: http://hdl.handle.net/2128/20514 doi:10.1523/JNEUROSCI.5066-06.2007

Abstract: It is currently hypothesized that adenosine is involved in the induction of sleep after prolonged wakefulness. This effect is partially reversed by the application of caffeine, which is a nonselective blocker of adenosine receptors. Here, we report that the most abundant and highly concentrated A1 subtype of cerebral adenosine receptors is upregulated after 24 h of sleep deprivation. We used the highly selective A1 adenosine receptor (A1AR) radioligand [18F]CPFPX ([18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine) and quantitative positron emission tomography to assess cerebral A1ARs before and after sleep deprivation in 12 healthy volunteers and a control group (n = 10) with regular sleep. In sleep deprived subjects, we found an increase of the apparent equilibrium total distribution volume in a region-specific pattern in all examined brain regions with a maximum increase in the orbitofrontal cortex (15.3%; p = 0.014). There were no changes in the control group with regular sleep. This is the first molecular imaging study that provides in vivo evidence for an A1AR upregulation in cortical and subcortical brain regions after prolonged wakefulness, indicating that A1AR expression is contributing to the homeostatic sleep regulation.

Keyword(s): Adult (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Positron-Emission Tomography (MeSH) ; Receptor, Adenosine A1: metabolism (MeSH) ; Sleep Deprivation: metabolism (MeSH) ; Sleep Deprivation: radionuclide imaging (MeSH) ; Receptor, Adenosine A1 ; J ; imaging (auto) ; adenosine A(1) receptor (auto) ; positron emission tomography (auto) ; [F-18]CPFPX (auto) ; sleep deprivation (auto) ; human (auto)