Impact of recovery sleep after sleep deprivation on cerebral A1 adenosine receptor densityElmenhorst D1, Elmenhorst EM2, Kroll T1, Matusch A1 Aeschbach D2 and Bauer A1,3 1 Forschungszentrum Jülich, Institute of Neuroscience and Medicine 2, Jülich, Germany, 2 German Aerospace Center, Institute of aerospace medicine, Cologne Germany, 3 Heinrich Heine University Düsseldorf, Medical Faculty, Neurological Department, Düsseldorf, Germany Objectives: Sleep loss triggers a reaction of the homeostatic sleep regulatory system in which adenosine is believed to play a key role. The brain adenosine concentration increases during wakefulness thereby inducing sleepiness [1]. If wakefulness is extended by sleep deprivation, this increase is accompanied by an up-regulation of adenosine receptor density [2].Previously, we found in subjects deprived of sleep for 28 hours, an increase of the distribution volume (VT) of the highly selective A1 adenosine receptor (A1AR) radioligand 18F CPFPX in a region-specific pattern in several brain regions (maximum: orbitofrontal cortex 15.3%, p=0.014, n=12). Whereas there were no significant changes (1.5%) in a control group (n=10) with regular sleep between both scans [2].The objective of the current study was to investigate if an extension of the wake period to 58 hours leads to a further increase of A1AR densities and if subsequent recovery sleep restores baseline levels of receptor densities.Methods: 15 healthy male volunteers participated in a dynamic 18F CPFPX bolus/infusions-PET study with blood sampling and metabolite correction. Subjects were scanned after 58 hours of sustained wakefulness and after 14 hours of recovery sleep at the same time of day on consecutive days under identical conditions.Regional VT were determined by calculating the tissue to plasma ratio during the steady state phase.Results: The distribution volumes after sleep deprivation (e.g. VT=0.83, orbitofrontal cortex) were found to be significantly higher than after the recovery sleep condition in all (sub)cortical regions investigated (10-14%, p=0.001-0.008). Compared to the baseline group of the preceding experiment (VT=0.73, n=22) the receptor density after recovery sleep (VT=0.72) was not significantly different. Conclusions: This study demonstrates that a single night of recovery sleep returns the increased A1AR availability in the human brain after prolonged sleep deprivation back to the level of normal sleeping controls. These findings support the general hypothesis of an increase in synaptic strength during wakefulness and downscaling during normal sleep as a maintenance mechanism of synaptic functionality. Research support: References: [1] Porkka-Heiskanen et al. 1997 Science 276:1265–1268[2]Elmenhorst D et al. J Neuroscience 2007; 27(9):2410 –241
