title: Convergent effects of acute stress and glucocorticoid exposure upon MAO-A in humans.
abstract: Monoamine oxidase-A (MAO-A), a key brain enzyme which metabolizes monoamines, is implicated in the pathophysiology of stress-related illnesses, including major depressive disorder, addiction, and violent behavior. Chronic stressors and glucocorticoid-administration typically associate with elevated MAO-A levels/activity. However, the relationship of shorter stress or glucocorticoid exposures and MAO-A levels/activity is not well established. Our objectives are to assess effects of acute stress upon MAO-A V(T,) an index of MAO-A density, in human brain and acute glucocorticoid exposure upon MAO-A levels in human neuronal and glial cell lines. Twelve healthy, non-smoking participants aged 18-50 underwent [(11)C]harmine positron emission tomography to measure brain MAO-A V(T) on two different days: One under acute psychosocial stress (via Trier Social Stress and Montreal Imaging Stress Tasks) and one under a non-stress condition. MAO-A density (by Western blot) and activity (by [(14)C]-5-HT metabolism and liquid scintillation spectroscopy) were measured in human neuronal and glial cell lines after 4 h exposure to dexamethasone. We observed a significant reduction in whole-brain MAO-A binding as reflected by reductions in 10 of 11 brain regions. Acute dexamethasone exposure in neuronal and glial cells significantly decreased MAO-A activity and protein levels. We observed a highly consistent relationship between acute stressors and glucocorticoid administration and decreased MAO-A binding, activity and protein levels. Since MAO-A metabolizes monoamines, this phenomenon may explain why acute stressors benefit healthy animals even though chronic stress is associated with illness.
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario M5T 1R8, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Soliman
authors.forename: Chinelo
authors.initials: C
authors.lastname: Udemgba
authors.forename: Ian
authors.initials: I
authors.lastname: Fan
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Laura
authors.initials: L
authors.lastname: Miler
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Jens
authors.initials: J
authors.lastname: Pruessner
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ou
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011877:Radionuclide Imaging; D013315:Stress, Psychological / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D008995:Monoamine Oxidase; D006854:Hydrocortisone