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Convergent Effects of Acute Stress and Glucocorticoid Exposure upon MAO-A in Humans

2012; Society for Neuroscience; Volume: 32; Issue: 48 Linguagem: Inglês

10.1523/jneurosci.2091-12.2012

1529-2401

Alexandra Soliman, Chinelo Udemgba, Ian Fan, Xin Xu, Laura Miler, Pablo Rusjan, Sylvain Houle, Alan A. Wilson, Jens C. Pruessner, Xiao‐Ming Ou, Jeffrey H. Meyer,

Neurotransmitter Receptor Influence on Behavior

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.