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Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress

Since the pioneering discovery of the rapid CNS depressant actions of steroids by the “father of stress,” Hans Seyle 70 years ago, brain-derived “neurosteroids” have emerged as powerful endogenous modulators of neuronal excitability. The majority of the intervening research has focused on a class of...

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Autores principales: Gunn, Benjamin G., Brown, Adam R., Lambert, Jeremy J., Belelli, Delia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230140/
https://www.ncbi.nlm.nih.gov/pubmed/22164129
http://dx.doi.org/10.3389/fnins.2011.00131
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author Gunn, Benjamin G.
Brown, Adam R.
Lambert, Jeremy J.
Belelli, Delia
author_facet Gunn, Benjamin G.
Brown, Adam R.
Lambert, Jeremy J.
Belelli, Delia
author_sort Gunn, Benjamin G.
collection PubMed
description Since the pioneering discovery of the rapid CNS depressant actions of steroids by the “father of stress,” Hans Seyle 70 years ago, brain-derived “neurosteroids” have emerged as powerful endogenous modulators of neuronal excitability. The majority of the intervening research has focused on a class of naturally occurring steroids that are metabolites of progesterone and deoxycorticosterone, which act in a non-genomic manner to selectively augment signals mediated by the main inhibitory receptor in the CNS, the GABA(A) receptor. Abnormal levels of such neurosteroids associate with a variety of neurological and psychiatric disorders, suggesting that they serve important physiological and pathophysiological roles. A compelling case can be made to implicate neurosteroids in stress-related disturbances. Here we will critically appraise how brain-derived neurosteroids may impact on the stress response to acute and chronic challenges, both pre- and postnatally through to adulthood. The pathological implications of such actions in the development of psychiatric disturbances will be discussed, with an emphasis on the therapeutic potential of neurosteroids for the treatment of stress-associated disorders.
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spelling pubmed-32301402011-12-07 Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress Gunn, Benjamin G. Brown, Adam R. Lambert, Jeremy J. Belelli, Delia Front Neurosci Neuroscience Since the pioneering discovery of the rapid CNS depressant actions of steroids by the “father of stress,” Hans Seyle 70 years ago, brain-derived “neurosteroids” have emerged as powerful endogenous modulators of neuronal excitability. The majority of the intervening research has focused on a class of naturally occurring steroids that are metabolites of progesterone and deoxycorticosterone, which act in a non-genomic manner to selectively augment signals mediated by the main inhibitory receptor in the CNS, the GABA(A) receptor. Abnormal levels of such neurosteroids associate with a variety of neurological and psychiatric disorders, suggesting that they serve important physiological and pathophysiological roles. A compelling case can be made to implicate neurosteroids in stress-related disturbances. Here we will critically appraise how brain-derived neurosteroids may impact on the stress response to acute and chronic challenges, both pre- and postnatally through to adulthood. The pathological implications of such actions in the development of psychiatric disturbances will be discussed, with an emphasis on the therapeutic potential of neurosteroids for the treatment of stress-associated disorders. Frontiers Research Foundation 2011-12-05 /pmc/articles/PMC3230140/ /pubmed/22164129 http://dx.doi.org/10.3389/fnins.2011.00131 Text en Copyright © 2011 Gunn, Brown, Lambert and Belelli. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Neuroscience
Gunn, Benjamin G.
Brown, Adam R.
Lambert, Jeremy J.
Belelli, Delia
Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress
title Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress
title_full Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress
title_fullStr Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress
title_full_unstemmed Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress
title_short Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress
title_sort neurosteroids and gaba(a) receptor interactions: a focus on stress
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230140/
https://www.ncbi.nlm.nih.gov/pubmed/22164129
http://dx.doi.org/10.3389/fnins.2011.00131
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