da Nature Review

Review

Nature Reviews Neuroscience 13, 22-37 (January 2012) | doi:10.1038/nrn3138

The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission

Maurizio Popoli¹, Zhen Yan², Bruce S. McEwen³ & Gerard Sanacora⁴  About the authors

Summary

• Excitatory synapses in the brain, which use glutamate as the primary neurotransmitter, represent a crucial target for the action of stress and its mediators. Mounting evidence suggests that stress, along with the associated hormonal and neurochemical mediators (particularly glucocorticoids), induces changes in glutamate release, transmission and metabolism in cortical and limbic brain areas, thereby influencing cognitive and emotional processing and behaviour.
• Depending on age, gender, duration and the type of the stressors experienced, stress may either have beneficial effects on cognitive and emotional functions or induce noxious and maladaptive changes in brain tissue, which have been linked to the development of neuropsychiatric disorders.
• Acute stress enhances glutamatergic synaptic transmission in the prefrontal cortex and other limbic regions, thereby facilitating certain cognitive functions.
• Acute stress increases glutamate release, membrane trafficking of AMPA and NMDA receptors, and potentially glutamate clearance in the prefrontal cortex through various mechanisms that involve glucocorticoid regulation.
• Chronic stress has been associated with a loss of glutamate receptors, impaired glutamate cycling and a suppression of glutamate transmission that may be attributable to the observed impairment of prefrontal cortex-dependent cognitive functions.
• These findings suggest that a new line of drug development aimed at minimizing the effects of chronic stress exposure on the function of the glutamatergic neurotransmitter system may prove beneficial in clinical settings. Straightforward pharmacological intervention on different regulatory sites of the glutamate synapse is a possible strategy for bypassing the unmet therapeutic needs posed by traditional drugs based on monoaminergic mechanisms.

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Author affiliations

1. Center of Neuropharmacology, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy.
2. Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York 14214, USA.
3. Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10065, USA.
4. Department of Psychiatry, Clinical Neuroscience Research Unit, Yale University School of Medicine, New Haven, Connecticut 06511, USA.

Correspondence to: Gerard Sanacora⁴ Email: gerard.sanacora@yale.edu

Published online 30 November 2011

orso castano : ancora una conferma sul fatto che lo stress incide sull'insorgenza del disturbo psichiatrico. Ancora un richiamo per "i fossili della psichiatria fossile"  ce e' indispensabile intervenire sui fattori predisponenti, cioe'  bisogna fare prevenzione secondaria. Ancora una volta il chiodo fisso della misurazione dei disturbi ormai conclamati oscurera' la scena della prevenzione secondaria in psichiatria!!