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: Alexandra Soliman, Chinelo Udemgba, Ian Fan, Xin Xu, Laura Miler, Pablo Rusjan, Sylvain Houle, Alan A Wilson, Jens Pruessner, Xiao-Ming Ou, Jeffrey H Meyer
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 32 Issue 48 Pg. 17120-7 (Nov 28 2012) ISSN: 1529-2401 [Electronic] United States
• PMID: 23197705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Dexamethasone
• Monoamine Oxidase
• Hydrocortisone

Topics

• Adult
• Brain (diagnostic imaging, drug effects, metabolism)
• Cell Line, Tumor
• Dexamethasone (pharmacology)
• Female
• Glucocorticoids (pharmacology)
• Humans
• Hydrocortisone (blood)
• Male
• Middle Aged
• Monoamine Oxidase (metabolism)
• Neuroglia (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Radionuclide Imaging
• Stress, Psychological (diagnostic imaging, metabolism)