Cerebral A1 adenosine receptor availability in female and male participants and its relationship to sleep
Anna L. Pierling,
Eva-Maria Elmenhorst,
Denise Lange,
Eva Hennecke,
Diego M. Baur,
Simone Beer,
Tina Kroll,
Bernd Neumaier,
Daniel Aeschbach,
Andreas Bauer,
Hans-Peter Landolt,
David Elmenhorst
Affiliations
Anna L. Pierling
Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany; Department of Neurophysiology, RWTH Aachen University, Institute of Zoology (Bio-II), Worringerweg 3, Aachen, North Rhine-Westphalia 52074, Germany; Corresponding authors at: Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany.
Eva-Maria Elmenhorst
German Aerospace Center, Institute of Aerospace Medicine, Linder Höhe, 51147 Cologne, North Rhine-Westphalia, Germany; RWTH Aachen University Hospital, Institute for Occupational, Social and Environmental Medicine, Pauwelsstrasse 30, Aachen, North Rhine-Westphalia 52074, Germany
Denise Lange
German Aerospace Center, Institute of Aerospace Medicine, Linder Höhe, 51147 Cologne, North Rhine-Westphalia, Germany
Eva Hennecke
German Aerospace Center, Institute of Aerospace Medicine, Linder Höhe, 51147 Cologne, North Rhine-Westphalia, Germany
Diego M. Baur
University of Zurich, Institute of Pharmacology and Toxicology, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Simone Beer
Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany
Tina Kroll
Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany
Bernd Neumaier
Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-5), Wilhelm-Johnen-Straße, Jülich, North Rhine-Westphalia 52428, Germany
Daniel Aeschbach
German Aerospace Center, Institute of Aerospace Medicine, Linder Höhe, 51147 Cologne, North Rhine-Westphalia, Germany; Division of Sleep Medicine, Harvard Medical School, Suite BL-438, 221 Longwood Avenue, Boston, MA 02115, United States; Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, Bonn, North Rhine-Westphalia 53127, Germany
Andreas Bauer
Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany; Medical Faculty, Department of Neurology, Heinrich-Heine University Düsseldorf, Moorenstrasse 5, Düsseldorf, North Rhine-Westphalia 40225, Germany
Hans-Peter Landolt
University of Zurich, Institute of Pharmacology and Toxicology, Winterthurerstrasse 190, 8057 Zurich, Switzerland
David Elmenhorst
Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany; Division of Medical Psychology, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, Bonn, North Rhine-Westphalia 53127, Germany; Multimodal Neuroimaging Group, Department of Nuclear Medicine, University Hospital Cologne, Kerpener Strasse 62, Cologne, North Rhine-Westphalia 50937, Germany; Corresponding authors at: Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany.
The neuromodulator adenosine and its receptors are mediators of sleep-wake regulation which is known to differ between sexes. We, therefore, investigated sex differences in A1 adenosine receptor (A1AR) availability in healthy human subjects under well-rested conditions using [18F]CPFPX and positron emission tomography (PET). [18F]CPFPX PET scans were acquired in 50 healthy human participants (20 females; mean age ± SD 28.0 ± 5.3 years). Mean binding potential (BPND; Logan's reference tissue model with cerebellum as reference region) and volume of distribution (VT) values were calculated in 12 and 15 grey matter brain regions, respectively. [18F]CPFPX BPND was higher in females compared to males in all investigated brain regions (p < 0.025). The largest differences were found in the pallidum and anterior cingulate cortex, where mean BPND values were higher by 29% in females than in males. In females, sleep efficiency correlated positively and sleep latency negatively with BPND in most brain regions. VT values did not differ between sexes. Sleep efficiency correlated positively with VT in most brain regions in female participants. In conclusion, our analysis gives a first indication for potential sex differences in A1AR availability even under well-rested conditions. A1AR availability as measured by [18F]CPFPX BPND is higher in females compared to males. Considering the involvement of adenosine in sleep-wake control, this finding might partially explain the known sex differences in sleep efficiency and sleep latency.
