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Review

Neurosteroids and Focal Epileptic Disorders

1
Montreal Neurological Institute-Hospital & Department of Neurology and Neurosurgery, 3801 University Street, Montreal, QC H3A 2B4, Canada
2
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Università 4, 41121 Modena, Italy
3
Department of Physiology, McGill University, Montreal, QC H3A 2B4, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249391
Received: 28 September 2020 / Revised: 27 November 2020 / Accepted: 8 December 2020 / Published: 10 December 2020
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids—allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)—are known to modulate GABAA receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABAA signaling in epileptic disorders, neurosteroids have profound effects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the effects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80–500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders. View Full-Text
Keywords: neurosteroids; epilepsy; allopregnanolone; allotetrahydrodeoxycorticosterone; GABA; epileptogenesis; ictogenesis neurosteroids; epilepsy; allopregnanolone; allotetrahydrodeoxycorticosterone; GABA; epileptogenesis; ictogenesis
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MDPI and ACS Style

Lévesque, M.; Biagini, G.; Avoli, M. Neurosteroids and Focal Epileptic Disorders. Int. J. Mol. Sci. 2020, 21, 9391. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249391

AMA Style

Lévesque M, Biagini G, Avoli M. Neurosteroids and Focal Epileptic Disorders. International Journal of Molecular Sciences. 2020; 21(24):9391. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249391

Chicago/Turabian Style

Lévesque, Maxime, Giuseppe Biagini, and Massimo Avoli. 2020. "Neurosteroids and Focal Epileptic Disorders" International Journal of Molecular Sciences 21, no. 24: 9391. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249391

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