Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 24, Pages -Publisher
MDPI
DOI: 10.3390/ijms21249391
Keywords
neurosteroids; epilepsy; allopregnanolone; allotetrahydrodeoxycorticosterone; GABA; epileptogenesis; ictogenesis
Funding
- Canadian Institutes of Health Research (CIHR) [8109, 74609, 130328]
- Savoy Foundation
Ask authors/readers for more resources
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(A) receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABA(A) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available