A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain

Naemi L Tichelman; Anna L Foerges; Eva-Maria Elmenhorst; Denise Lange; Eva Hennecke; Diego M Baur; Simone Beer; Tina Kroll; Bernd Neumaier; Andreas Bauer; Hans-Peter Landolt; Daniel Aeschbach; David Elmenhorst

doi:10.1016/j.neuroimage.2023.120345

A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A₁ adenosine receptor availability in the human brain

Neuroimage. 2023 Oct 15:280:120345. doi: 10.1016/j.neuroimage.2023.120345. Epub 2023 Aug 23.

Authors

Affiliations

¹ Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany.
² Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany; RWTH Aachen University, Department of Neurophysiology, Institute of Zoology (Bio-II), Worringerweg 3, Aachen, North Rhine-Westphalia 52074, Germany.
³ German Aerospace Center, Institute of Aerospace Medicine, Linder Höhe, Cologne, North Rhine-Westphalia 51147, Germany; Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Aachen, North Rhine-Westphalia 52074, Germany.
⁴ German Aerospace Center, Institute of Aerospace Medicine, Linder Höhe, Cologne, North Rhine-Westphalia 51147, Germany.
⁵ University of Zurich, Institute of Pharmacology & Toxicology, Winterthurerstrasse 190, Zurich 8057, Switzerland and Sleep & Health Zurich, University Center of Competence, University of Zurich, Zurich, Switzerland.
⁶ Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-5), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany.
⁷ German Aerospace Center, Institute of Aerospace Medicine, Linder Höhe, Cologne, North Rhine-Westphalia 51147, Germany; Harvard Medical School, Division of Sleep Medicine, Suite BL-438, 221 Longwood Avenue, Boston, Massachusetts 02115, United States of America; Rheinische Friedrich-Wilhelms-Universität Bonn, Institute of Experimental Epileptology and Cognition Research, University of Bonn Medical Center, Sigmund-Freud Str. 25, Bonn, North Rhine-Westphalia 53127, Germany.
⁸ Forschungszentrum Jülich, Institute of Neuroscience and Medicine (INM-2), Wilhelm-Johnen-Strasse, Jülich, North Rhine-Westphalia 52428, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Division of Medical Psychology, Venusberg-Campus 1, Bonn, North Rhine-Westphalia 53127, Germany; University Hospital Cologne, Multimodal Neuroimaging Group, Department of Nuclear Medicine, Kerpener Strasse 62, Cologne, North Rhine-Westphalia 50937, Germany. Electronic address: d.elmenhorst@fz-juelich.de.

PMID: 37625500
DOI: 10.1016/j.neuroimage.2023.120345

Abstract

The EEG alpha rhythm (∼ 8-13 Hz) is one of the most salient human brain activity rhythms, modulated by the level of attention and vigilance and related to cerebral energy metabolism. Spectral power in the alpha range in wakefulness and sleep strongly varies among individuals based on genetic predisposition. Knowledge about the underlying genes is scarce, yet small studies indicated that the variant rs5751876 of the gene encoding A_2A adenosine receptors (ADORA2A) may contribute to the inter-individual variation. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate breakdown and acts as a sleep promoting molecule by activating A₁ and A_2A adenosine receptors. We performed sleep and positron emission tomography studies in 59 healthy carriers of different rs5751876 alleles, and quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A₁ adenosine receptor availability with ¹⁸F-CPFPX. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F_(18,37) = 2.35, p = 0.014, Wilk's Λ = 0.487). Furthermore, a modulatory effect of ADORA2A genotype on A₁ adenosine receptor binding potential was found across all considered brain regions (F_(18,40) = 2.62, p = 0.006, Wilk's Λ = 0.459), which remained significant for circumscribed occipital region of calcarine fissures after correction for multiple comparisons. In female participants, a correlation between individual differences in oscillatory alpha power and A₁ receptor availability was observed. In conclusion, we confirmed that a genetic variant of ADORA2A affects individual alpha power, while a direct modulatory effect via A₁ adenosine receptors in females is suggested.

Keywords: ADORA2A; Adenosine receptor; Alpha power; EEG; Human; Positron emission tomography; Sleep-wake regulation; [18F]CPFPX.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine
Brain* / diagnostic imaging
Electroencephalography
Female
Genetic Variation
Humans
Male
Receptor, Adenosine A2A* / genetics

Substances

Adenosine
ADORA2A protein, human
Receptor, Adenosine A2A