title: Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors.
abstract: Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal-medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.
authors.affiliation: Hospital of the University of Munich (LMU), Marchioninistrasse15, D-81377 Munich, Germany. Electronic address: bootsing.yi@gmail.com.
authors.forename: Buqing
authors.initials: B
authors.lastname: Yi
authors.affiliation: Institute of Biomedical Problems, 123007 Moscow, Russian Federation.
authors.forename: Igor
authors.initials: I
authors.lastname: Nichiporuk
authors.affiliation: University of Burgundy, SPMS (EA 4180), 21000 Dijon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Nicolas
authors.affiliation: Institute of Movement and Neurosciences, German Sport University Cologne, 50933 Cologne, Germany; Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, Queensland, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Hospital of the University of Munich (LMU), Marchioninistrasse15, D-81377 Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Feuerecker
authors.affiliation: Institute of Biomedical Problems, 123007 Moscow, Russian Federation.
authors.forename: Galina
authors.initials: G
authors.lastname: Vassilieva
authors.affiliation: Institute of Doping Analysis and Sports Biochemistry, D-01731 Dresden, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Thieme
authors.affiliation: Hospital of the University of Munich (LMU), Marchioninistrasse15, D-81377 Munich, Germany. Electronic address: Gustav.Schelling@med.uni-muenchen.de.
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
authors.affiliation: Hospital of the University of Munich (LMU), Marchioninistrasse15, D-81377 Munich, Germany. Electronic address: alexander.chouker@med.uni-muenchen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Choukèr
mesh_terms: D000328:Adult; D001095:Arachidonic Acids / Q000097:blood*; D001921:Brain / Q000503:physiopathology; D002395:Catecholamines / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004569:Electroencephalography; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D005989:Glycerides / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D016014:Linear Models; D008297:Male; D011569:Psychiatric Status Rating Scales; D013315:Stress, Psychological / Q000097:blood* / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D053719:Tandem Mass Spectrometry
chemical_list: D001095:Arachidonic Acids; D002395:Catecholamines; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate
keywords: 2-Arachidonoylglycerol; Chronic stress; Endocannabinoid; HPA axis; N-arachidonylethanolamine