Human blood adenosine biomarkers and non-rapid eye movement sleep stage 3 (NREM3) cortical functional connectivity associations during a 30-day head-down-tilt bed rest analogue: Potential effectiveness of a reactive sledge jump as a countermeasure

J Sleep Res. 2021 Oct;30(5):e13323. doi: 10.1111/jsr.13323. Epub 2021 Apr 7.


We investigated the alterations of sleep regulation and promotion biomarkers as adenosine through its enzymes total adenosine deaminase (tADA)/adenosine deaminase (ADA2) in a microgravity analogue environment of head-down-tilt bed rest and their association with brain connectivity networks during non-rapid eye movement sleep stage 3 (NREM3), as well as the effectiveness of the reactive sledge (RSL) jump countermeasure to promote sleep. A total of 23 healthy male volunteers were maintained in 6° head-down-tilt position for 30 days and assigned either to a control or to a RSL group. Blood collection and polysomnographic recordings were performed on data acquisition day 1, 14, 30 and -14, 21, respectively. Immunochemical techniques and network-based statistics were employed for adenosine enzymes and cortical connectivity estimation. Our findings indicate that human blood adenosine biomarkers as well as NREM3 cortical functional connectivity are impaired in simulated microgravity. RSL physical activity intervened in sleep quality via tADA/ADA2 fluctuations lack, minor cortical connectivity increases, and limited degree of node and resting-state networks. Statistically significant decreases in adenosine biomarkers and NREM3 functional connectivity involving regions (left superior temporal gyrus, right postcentral gyrus, precuneus, left middle frontal gyrus, left postcentral gyrus, left angular gyrus and precuneus) of the auditory, sensorimotor default-mode and executive networks highlight the sleep disturbances due to simulated microgravity and the sleep-promoting role of RSL countermeasure. The head-down-tilt environment led to sleep deterioration projected through NREM3 cortical brain connectivity or/and adenosine biomarkers shift. This decline was more pronounced in the absence of the RSL countermeasure, thereby highlighting its likely exploitation during space missions.

Keywords: brain; indicators; metabolic; microgravity; physical activity; simulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine*
  • Bed Rest*
  • Biomarkers
  • Head-Down Tilt
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Rest
  • Sleep Stages


  • Biomarkers
  • Adenosine