Neurosteroids and Focal Epileptic Disorders

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 GABA...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-12, Vol.21 (24), p.9391
Main Authors: Lévesque, Maxime, Biagini, Giuseppe, Avoli, Massimo
Format: Article
Language:English
Subjects:
Animal models
Animals
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Brain slice preparation
Brain Waves - drug effects
Cholesterol
Epilepsy
Epilepsy, Temporal Lobe - drug therapy
Epilepsy, Temporal Lobe - metabolism
Epilepsy, Temporal Lobe - physiopathology
Firing pattern
Glial cells
Humans
Neuronal-glial interactions
Neurosteroids
Neurosteroids - pharmacology
Neurosteroids - therapeutic use
Oscillations
Pregnanolone
Pregnenolone
Review
Seizures
Synaptic Transmission - drug effects
Synchronism
Synchronization
Temporal lobe
γ-Aminobutyric acid A receptors
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Summary: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 GABA receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABA 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21249391