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Biomolecular Concepts

Editor-in-Chief: Di Cera, Enrico


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CiteScore 2017: 2.50

SCImago Journal Rank (SJR) 2017: 0.861
Source Normalized Impact per Paper (SNIP) 2017: 0.722

ICV 2017: 131.30

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Online
ISSN
1868-503X
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Volume 4, Issue 1

Issues

Neurosteroids and GABAergic signaling in health and disease

Georgina MacKenzie / Jamie Maguire
Published Online: 2012-11-16 | DOI: https://doi.org/10.1515/bmc-2012-0033

Abstract

Endogenous neurosteroids such as allopregnanolone, allotetrahydrodeoxycorticosterone, and androstanediol are synthesized either de novo in the brain from cholesterol or are generated from the local metabolism of peripherally derived progesterone or corticosterone. Fluctuations in neurosteroid concentrations are important in the regulation of a number of physiological responses including anxiety and stress, reproductive, and sexual behaviors. These effects are mediated in part by the direct binding of neurosteroids to γ-aminobutyric acid type-A receptors (GABAARs), resulting in the potentiation of GABAAR-mediated currents. Extrasynaptic GABAARs containing the δ subunit, which contribute to the tonic conductance, are particularly sensitive to low nanomolar concentrations of neurosteroids and are likely their preferential target. Considering the large charge transfer generated by these persistently open channels, even subtle changes in neurosteroid concentrations can have a major impact on neuronal excitability. Consequently, aberrant levels of neurosteroids have been implicated in numerous disorders, including, but not limited to, anxiety, neurodegenerative diseases, alcohol abuse, epilepsy, and depression. Here we review the modulation of GABAAR by neurosteroids and the consequences for health and disease.

Keywords: allopregnanolone; γ-aminobutyric acid (GABA); neurosteroids; allotetrahydrodeoxycorticosterone (THDOC)

About the article

Georgina MacKenzie

Georgina MacKenzie received her bachelor’s degree in Biochemistry from the University of Bath (Bath, UK) in 2006. She then moved to Imperial College London (London, UK) where she completed a Master’s degree in Biochemical Research in 2007 before pursuing a PhD in Neuroscience under the supervision of Dr Stephen Brickley. She was awarded her PhD in 2011 and is now undertaking her postdoctoral training with Dr Jamie Maguire in the Department of Neuroscience at Tufts University School of Medicine (Boston, MA, USA).

Jamie Maguire

Jamie Maguire received her bachelor’s degree in Neuroscience from the University of Pittsburgh (Pittsburgh, PA) in 1998 and then earned her PhD in Neuroscience in 2003 from The George Washington University (Washington, DC) under the mentorship of Dr. Margaret Sutherland. Jamie then trained as a postdoctoral fellow with Dr. Istvan Mody at the University of California, Los Angeles (Los Angeles, CA) prior to establishing her own laboratory in the Neuroscience Department at the Tufts University School of Medicine.


Corresponding author: Jamie Maguire, Department of Neuroscience, School of Medicine, Tufts University, Boston, MA 02111, USA


Received: 2012-07-30

Accepted: 2012-10-12

Published Online: 2012-11-16

Published in Print: 2013-02-01


Citation Information: BioMolecular Concepts, Volume 4, Issue 1, Pages 29–42, ISSN (Online) 1868-503X, ISSN (Print) 1868-5021, DOI: https://doi.org/10.1515/bmc-2012-0033.

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