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Neurosteroids and Extrasynaptic GABAA Receptors

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Extrasynaptic GABAA Receptors

Part of the book series: The Receptors ((REC,volume 27))

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Abstract

Steroid sex hormones are generally thought to act through intracellular receptors, where they regulate gene expression and protein synthesis, an effect that takes minutes to hours to occur. However, steroid metabolites can also directly modulate the activity of numerous ligand-gated ion channels. These metabolites can be synthesised de novo in the CNS, and are termed neurosteroids. The action of neurosteroids at ion channels, most notably GABAA receptors, is implicated in natural and pathophysiological stress responses and neurophysiological changes during the oestrous cycle and parturition. Here, I will review the synthesis, action and the activity of neurosteroids on synaptic and extrasynaptic GABAA receptors.

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Author information

Authors and Affiliations

  1. Neuroscience Division, Cardiff School of Biosciences, Cardiff University, The Sir Martin Evans Building, Museum Avenue, CF10 3AX, Cardiff, UK

    William M. Connelly

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  1. William M. Connelly
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Correspondence to William M. Connelly .

Editor information

Editors and Affiliations

  1. Neuroscience and Mental Health Research Institute, Institute of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, United Kingdom

    Adam C. Errington

  2. Dept. of Physiology & Biochemistry, University of Malta, Msida MSD, Malta

    Giuseppe Di Giovanni

  3. School of Biosciences, Cardiff University, Cardiff, United Kingdom

    Vincenzo Crunelli

Conclusion

Conclusion

In the 50 years since Selye’s report of the anaesthetic action of neurosteroids, much has been revealed about their action and physiological relevance. However, many important areas remain to be properly covered. Apart from the regulation of CRH release, what roles do neurosteroids play in the physiological response to stress? Is the action of neurosteroids enhanced or decreased in pregnancy? How is neurosteroid synthesis regulated in the CNS? It is still not completely clear which GABAA receptor subtypes neurosteroids target. There appears to be a dearth of molecular tools to investigate these questions (for instance, a CNS-specific knockout of 5α-reductase) and hopefully the development of tools like this will help elucidate the role of neurosteroids in the healthy and diseased brain.

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Connelly, W. (2014). Neurosteroids and Extrasynaptic GABAA Receptors. In: Errington, A., Di Giovanni, G., Crunelli, V. (eds) Extrasynaptic GABAA Receptors. The Receptors, vol 27. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1426-5_5

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