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

作者：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 · 发表于：Journal of Neuroscience · 年份：2012 · DOI：10.1523/jneurosci.2091-12.2012 · 被引用次数：37 · 研究领域：Stress Responses and Cortisol、Tryptophan and brain disorders、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...