Neurosteroidi ed epilettogenesi: evidenze a favore di una relazione tra induzione dell’enzima P450scc e durata della fase di latenza nel modello della pilocarpina.

Neurosteroids are GABAA receptor agonists able to modulate seizure susceptibility. They are mainly synthesizedin astrocytes, a type of glial cells that are activated by neuronal damage. Interestingly, status epilepticus (SE)induces neuronal damage and a chronic epileptic condition that becomes evident following a “latent” period,in which glial cells are highly activated. Investigating glial cell activation in the pilocarpine model, wefound that P450scc, the rate-limiting enzyme in neurosteroid synthesis, is upregulated in hippocampal astrocytesduring the latent period. The induction of P450scc immunoreactivity was stronger with prolonged statusepilepticus and was associated with longer latencies to the development of seizures, suggesting thatenhanced neurosteroid synthesis retards epileptogenesis. Accordingly, the 5α-reductase inhibitor finasteride,which blocks neurosteroid synthesis, reduced the latent period, thus indicating that glia-derived neurosteroidsmay be antiepileptogenic.