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Neurosteroid Regulation of Seizures: Role of GABAA Receptor Plasticity

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Book cover Antiepileptic Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Neurosteroids, which are derived from adrenal or gonadal steroid hormones or synthesized de novo from cholesterol in the brain, regulate neuronal excitability. Neurosteroids suppress seizures, and this action is particularly important in women with epilepsy, who may experience seizure exacerbation due to hormonal fluctuations associated with their menstrual cycle, called catamenial epilepsy. Neurosteroids exert their anticonvulsant action by increasing GABAA receptor-mediated fast inhibitory neurotransmission. However, the GABAA receptors expressed in epilepsy have altered subunit composition, such that higher concentrations of neurosteroids are required to enhance the inhibition. Despite advances in our understanding of the neurosteroid regulation of seizures via modulation of GABAA receptors, our knowledge of whether endogenous neurosteroid synthesis is altered by seizures or in epilepsy is incomplete. Furthermore, the molecular mechanisms that trigger the down-regulation of neurosteroid-sensitive GABAA receptors in epilepsy are not well understood. Insights into these aspects of neurosteroids and GABAA receptors could provide novel targets for the development of therapies aimed at a better management of seizures in women with epilepsy.

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Authors and Affiliations

  1. Department of Neurology, University of Virginia, Health Sciences Center, 800394, Charlottesville, VA, 22908, USA

    Suchitra Joshi Ph.D. & Jaideep Kapur M.D., Ph.D.

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  1. Suchitra Joshi Ph.D.
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  2. Jaideep Kapur M.D., Ph.D.
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Correspondence to Jaideep Kapur M.D., Ph.D. .

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  1. Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB) Faculty of Exact Sciences, National University of La Plata, La Plata, Buenos Aires, Argentina

    Alan Talevi

  2. Department of Pharmacobiology, Center for Research and Advanced Studies, Mexico City, Mexico

    Luisa Rocha

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Joshi, S., Kapur, J. (2016). Neurosteroid Regulation of Seizures: Role of GABAA Receptor Plasticity. In: Talevi, A., Rocha, L. (eds) Antiepileptic Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6355-3_7

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  • DOI: https://doi.org/10.1007/978-1-4939-6355-3_7

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