Neurosteroids as Endogenous Regulators of Seizure Susceptibility

The document explored the role of deoxycorticosterone (DOC)-derived neurosteroids in modulating GABA A receptor function and seizure susceptibility under stress. It was found that stress increased the synthesis of DOC, which is metabolized into neurosteroids like THDOC with anticonvulsant properties. In rats, stress elevated THDOC levels and increased seizure thresholds, effects that were reversed by finasteride, a 5α-reductase inhibitor. DOC also protected mice against various seizures, with its effects being partially reversed by indomethacin. Additionally, the study highlighted that the GABA A receptor δ subunit increased sensitivity to neurosteroid modulation, with THDOC significantly enhancing receptor currents, particularly in the α1β38 isoform. These findings suggested that DOC-derived neurosteroids could mediate stress-induced changes in seizure susceptibility through their action on GABA A receptors.